Full text data of CA2
CA2
[Confidence: high (present in two of the MS resources)]
Carbonic anhydrase 2; 4.2.1.1 (Carbonate dehydratase II; Carbonic anhydrase C; CAC; Carbonic anhydrase II; CA-II)
Carbonic anhydrase 2; 4.2.1.1 (Carbonate dehydratase II; Carbonic anhydrase C; CAC; Carbonic anhydrase II; CA-II)
hRBCD
IPI00218414
IPI00218414 carbonic anhydrase II carbonic anhydrase II membrane n/a n/a n/a n/a n/a n/a n/a n/a 2 n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a membrane bound n/a found at its expected molecular weight found at molecular weight
IPI00218414 carbonic anhydrase II carbonic anhydrase II membrane n/a n/a n/a n/a n/a n/a n/a n/a 2 n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a membrane bound n/a found at its expected molecular weight found at molecular weight
UniProt
P00918
ID CAH2_HUMAN Reviewed; 260 AA.
AC P00918; B2R7G8; Q6FI12; Q96ET9;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 180.
DE RecName: Full=Carbonic anhydrase 2;
DE EC=4.2.1.1;
DE AltName: Full=Carbonate dehydratase II;
DE AltName: Full=Carbonic anhydrase C;
DE Short=CAC;
DE AltName: Full=Carbonic anhydrase II;
DE Short=CA-II;
GN Name=CA2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3108857; DOI=10.1093/nar/15.11.4687;
RA Montgomery J.C., Venta P.J., Tashian R.E., Hewett-Emmett D.;
RT "Nucleotide sequence of human liver carbonic anhydrase II cDNA.";
RL Nucleic Acids Res. 15:4687-4687(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3121496; DOI=10.1016/0888-7543(87)90008-5;
RA Murakami H., Marelich G.P., Grubb J.H., Kyle J.W., Sly W.S.;
RT "Cloning, expression, and sequence homologies of cDNA for human
RT carbonic anhydrase II.";
RL Genomics 1:159-166(1987).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S.,
RA Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W.,
RA Korn B., Zuo D., Hu Y., LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Urinary bladder;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ovary;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PROTEIN SEQUENCE OF 2-260.
RX PubMed=4207120;
RA Lin K.-T.D., Deutsch H.F.;
RT "Human carbonic anhydrases. XII. The complete primary structure of the
RT C isozyme.";
RL J. Biol. Chem. 249:2329-2337(1974).
RN [8]
RP PROTEIN SEQUENCE OF 2-260.
RX PubMed=823150;
RA Henderson L.E., Henriksson D., Nyman P.O.;
RT "Primary structure of human carbonic anhydrase C.";
RL J. Biol. Chem. 251:5457-5463(1976).
RN [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-77.
RX PubMed=3000449; DOI=10.1016/0167-4781(85)90006-5;
RA Venta P.J., Montgomery J.C., Hewett-Emmett D., Tashian R.E.;
RT "Comparison of the 5' regions of human and mouse carbonic anhydrase II
RT genes and identification of possible regulatory elements.";
RL Biochim. Biophys. Acta 826:195-201(1985).
RN [10]
RP INTERACTION WITH SLC4A4.
RX PubMed=14567693; DOI=10.1021/bi0353124;
RA Alvarez B.V., Loiselle F.B., Supuran C.T., Schwartz G.J., Casey J.R.;
RT "Direct extracellular interaction between carbonic anhydrase IV and
RT the human NBC1 sodium/bicarbonate co-transporter.";
RL Biochemistry 42:12321-12329(2003).
RN [11]
RP INTERACTION WITH SLC4A7.
RX PubMed=14736710; DOI=10.1152/ajpcell.00382.2003;
RA Loiselle F.B., Morgan P.E., Alvarez B.V., Casey J.R.;
RT "Regulation of the human NBC3 Na+/HCO3- cotransporter by carbonic
RT anhydrase II and PKA.";
RL Am. J. Physiol. 286:C1423-C1433(2004).
RN [12]
RP INTERACTION WITH SLC4A4.
RX PubMed=15218065; DOI=10.1113/jphysiol.2004.065110;
RA Pushkin A., Abuladze N., Gross E., Newman D., Tatishchev S., Lee I.,
RA Fedotoff O., Bondar G., Azimov R., Ngyuen M., Kurtz I.;
RT "Molecular mechanism of kNBC1-carbonic anhydrase II interaction in
RT proximal tubule cells.";
RL J. Physiol. (Lond.) 559:55-65(2004).
RN [13]
RP FUNCTION, INTERACTION WITH SLC26A6, AND SUBCELLULAR LOCATION.
RX PubMed=15990874; DOI=10.1038/sj.emboj.7600736;
RA Alvarez B.V., Vilas G.L., Casey J.R.;
RT "Metabolon disruption: a mechanism that regulates bicarbonate
RT transport.";
RL EMBO J. 24:2499-2511(2005).
RN [14]
RP ENZYME REGULATION.
RX PubMed=17314045; DOI=10.1016/j.bmcl.2007.01.113;
RA Temperini C., Innocenti A., Guerri A., Scozzafava A., Rusconi S.,
RA Supuran C.T.;
RT "Phosph(on)ate as a zinc-binding group in metalloenzyme inhibitors: X-
RT ray crystal structure of the antiviral drug foscarnet complexed to
RT human carbonic anhydrase I.";
RL Bioorg. Med. Chem. Lett. 17:2210-2215(2007).
RN [15]
RP BIOPHYSICOCHEMICAL PROPERTIES, AND ENZYME REGULATION.
RX PubMed=18618712; DOI=10.1002/prot.22144;
RA Di Fiore A., Monti S.M., Hilvo M., Parkkila S., Romano V., Scaloni A.,
RA Pedone C., Scozzafava A., Supuran C.T., De Simone G.;
RT "Crystal structure of human carbonic anhydrase XIII and its complex
RT with the inhibitor acetazolamide.";
RL Proteins 74:164-175(2009).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
RX PubMed=4621826;
RA Liljas A., Kannan K.K., Bergsten P.-C., Waara I., Fridborg K.,
RA Strandberg B., Carlbom U., Jaerup L., Loevgren S., Petef M.;
RT "Crystal structure of human carbonic anhydrase C.";
RL Nature New Biol. 235:131-137(1972).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) IN COMPLEX WITH ZINC ION.
RX PubMed=3151019; DOI=10.1002/prot.340040406;
RA Eriksson A.E., Jones T.A., Liljas A.;
RT "Refined structure of human carbonic anhydrase II at 2.0-A
RT resolution.";
RL Proteins 4:274-282(1988).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) IN COMPLEX WITH ZINC ION AND
RP INHIBITORS.
RX PubMed=3151020; DOI=10.1002/prot.340040407;
RA Eriksson A.E., Kylsten P.M., Jones T.A., Liljas A.;
RT "Crystallographic studies of inhibitor binding sites in human carbonic
RT anhydrase II: a pentacoordinated binding of the SCN-ion to the zinc at
RT high pH.";
RL Proteins 4:283-293(1988).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF MUTANT SER-199 IN COMPLEX
RP WITH ZINC ION, MUTAGENESIS OF THR-199, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=1909891; DOI=10.1021/bi00102a005;
RA Krebs J.F., Fierke C.A., Alexander R.S., Christianson D.W.;
RT "Conformational mobility of His-64 in the Thr-200TO: human carbonic
RT anhydrase II.";
RL Biochemistry 30:9153-9160(1991).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF MUTANTS PHE-142; TYR-142 AND
RP HIS-142 IN COMPLEX WITH INHIBITORS, AND MUTAGENESIS OF VAL-142.
RX PubMed=1932029; DOI=10.1021/bi00110a008;
RA Alexander R.S., Nair S.K., Christianson D.W.;
RT "Engineering the hydrophobic pocket of carbonic anhydrase II.";
RL Biochemistry 30:11064-11072(1991).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF MUTANT ALA-121, MUTAGENESIS
RP OF VAL-121, ENZYME REGULATION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=1910042;
RA Nair S.K., Calderone T.L., Christianson D.W., Fierke C.A.;
RT "Altering the mouth of a hydrophobic pocket. Structure and kinetics of
RT human carbonic anhydrase II mutants at residue Val-121.";
RL J. Biol. Chem. 266:17320-17325(1991).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) IN COMPLEX WITH ZINC ION AND
RP INHIBITORS, AND ENZYME REGULATION.
RX PubMed=1336460; DOI=10.1111/j.1432-1033.1992.tb17490.x;
RA Mangani S., Haakansson K.;
RT "Crystallographic studies of the binding of protonated and
RT unprotonated inhibitors to carbonic anhydrase using hydrogen sulphide
RT and nitrate anions.";
RL Eur. J. Biochem. 210:867-871(1992).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (1.54 ANGSTROMS) IN COMPLEX WITH ZINC ION AND
RP INHIBITORS.
RX PubMed=1433293; DOI=10.1016/0022-2836(92)90531-N;
RA Haakansson K., Carlsson M., Svensson L.A., Liljas A.;
RT "Structure of native and apo carbonic anhydrase II and structure of
RT some of its anion-ligand complexes.";
RL J. Mol. Biol. 227:1192-1204(1992).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (1.88 ANGSTROMS) IN COMPLEX WITH COBALT ION AND
RP BICARBONATE.
RX PubMed=1474587; DOI=10.1016/0022-2836(92)90327-G;
RA Haakansson K., Wehnert A.;
RT "Structure of cobalt carbonic anhydrase complexed with bicarbonate.";
RL J. Mol. Biol. 228:1212-1218(1992).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF MUTANT CYS-94 IN COMPLEX
RP WITH ZINC ION, AND MUTAGENESIS OF HIS-94.
RX PubMed=8431430; DOI=10.1021/bi00057a015;
RA Alexander R.S., Kiefer L.L., Fierke C.A., Christianson D.W.;
RT "Engineering the zinc binding site of human carbonic anhydrase II:
RT structure of the His-94-->Cys apoenzyme in a new crystalline form.";
RL Biochemistry 32:1510-1518(1993).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF MUTANT ALA-197; GLU-197;
RP HIS-197 AND ARG-197, AND MUTAGENESIS OF LEU-197.
RX PubMed=8485129; DOI=10.1021/bi00068a005;
RA Nair S.K., Christianson D.W.;
RT "Structural consequences of hydrophilic amino acid substitutions in
RT the hydrophobic pocket of human carbonic anhydrase II.";
RL Biochemistry 32:4506-4514(1993).
RN [28]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF MUTANT CYS-198 IN COMPLEX
RP WITH ZINC ION, AND MUTAGENESIS OF THR-198.
RX PubMed=8399159; DOI=10.1021/bi00089a005;
RA Ippolito J.A., Christianson D.W.;
RT "Structure of an engineered His3Cys zinc binding site in human
RT carbonic anhydrase II.";
RL Biochemistry 32:9901-9905(1993).
RN [29]
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF MUTANT ALA-201 IN COMPLEX
RP WITH ZINC ION, AND MUTAGENESIS OF PRO-201.
RX PubMed=8218160; DOI=10.1021/bi00092a003;
RA Tweedy N.B., Nair S.K., Paterno S.A., Fierke C.A., Christianson D.W.;
RT "Structure and energetics of a non-proline cis-peptidyl linkage in a
RT proline-202-->alanine carbonic anhydrase II variant.";
RL Biochemistry 32:10944-10949(1993).
RN [30]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) IN COMPLEX WITH ZINC ION AND
RP INHIBITORS.
RX PubMed=8482389; DOI=10.1016/0014-5793(93)81565-H;
RA Joensson B.M., Haakansson K., Liljas A.;
RT "The structure of human carbonic anhydrase II in complex with bromide
RT and azide.";
RL FEBS Lett. 322:186-190(1993).
RN [31]
RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF MUTANT VAL-198 IN COMPLEX
RP WITH ZINC ION AND INHIBITORS, MUTAGENESIS OF THR-198, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=8262987;
RA Krebs J.F., Ippolito J.A., Christianson D.W., Fierke C.A.;
RT "Structural and functional importance of a conserved hydrogen bond
RT network in human carbonic anhydrase II.";
RL J. Biol. Chem. 268:27458-27466(1993).
RN [32]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) IN COMPLEX WITH INHIBITOR AND
RP ZINC ION.
RX PubMed=8331673; DOI=10.1006/jmbi.1993.1365;
RA Mangani S., Liljas A.;
RT "Crystal structure of the complex between human carbonic anhydrase II
RT and the aromatic inhibitor 1,2,4-triazole.";
RL J. Mol. Biol. 232:9-14(1993).
RN [33]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF MUTANT HIS-199 IN COMPLEX
RP WITH BICARBONATE AND ZINC ION, AND MUTAGENESIS OF THR-199.
RX PubMed=8451242; DOI=10.1002/prot.340150110;
RA Xue Y., Vidgren J., Svensson L.A., Liljas A., Jonsson B.H.,
RA Lindskog S.;
RT "Crystallographic analysis of Thr-200-->His human carbonic anhydrase
RT II and its complex with the substrate, HCO3-.";
RL Proteins 15:80-87(1993).
RN [34]
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF MUTANTS IN COMPLEX WITH
RP BICARBONATE AND ZINC ION, AND MUTAGENESIS OF GLU-106 AND THR-198.
RX PubMed=7901850; DOI=10.1002/prot.340170112;
RA Xue Y., Liljas A., Jonsson B.H., Lindskog S.;
RT "Structural analysis of the zinc hydroxide-Thr-199-Glu-106 hydrogen-
RT bond network in human carbonic anhydrase II.";
RL Proteins 17:93-106(1993).
RN [35]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) IN COMPLEX WITH COBALT; COPPER;
RP NICKEL AND MANGANESE IONS.
RX PubMed=15299481; DOI=10.1107/S0907444993008790;
RA Haakansson K., Wehnert A., Liljas A.;
RT "X-ray analysis of metal-substituted human carbonic anhydrase II
RT derivatives.";
RL Acta Crystallogr. D 50:93-100(1994).
RN [36]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) MUTANT GLN-106 IN COMPLEX WITH
RP THE INHIBITOR ACETATE, AND MUTAGENESIS OF GLU-106.
RX PubMed=15299482; DOI=10.1107/S0907444993009667;
RA Haakansson K., Briand C., Zaitsev V., Xue Y., Liljas A.;
RT "Wild-type and E106Q mutant carbonic anhydrase complexed with
RT acetate.";
RL Acta Crystallogr. D 50:101-104(1994).
RN [37]
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 2-259 OF MUTANTS ALA-94;
RP CYS-94; CYS-96; CYS-119 AND ASP-119 IN COMPLEX WITH ZINC ION.
RX PubMed=7803386; DOI=10.1021/bi00255a004;
RA Ippolito J.A., Christianson D.W.;
RT "Structural consequences of redesigning a protein-zinc binding site.";
RL Biochemistry 33:15241-15249(1994).
RN [38]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) IN COMPLEX WITH THE INHIBITOR
RP TRIFLUOROMETHANE SULPHONAMIDE.
RX PubMed=8070585; DOI=10.1016/0014-5793(94)00798-5;
RA Haakansson K., Liljas A.;
RT "The structure of a complex between carbonic anhydrase II and a new
RT inhibitor, trifluoromethane sulphonamide.";
RL FEBS Lett. 350:319-322(1994).
RN [39]
RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) IN COMPLEX WITH INHIBITORS.
RX PubMed=8142888; DOI=10.1002/pro.5560030115;
RA Smith G.M., Alexander R.S., Christianson D.W., McKeever B.M.,
RA Ponticello G.S., Springer J.P., Randall W.C., Baldwin J.J.,
RA Habecker C.N.;
RT "Positions of His-64 and a bound water in human carbonic anhydrase II
RT upon binding three structurally related inhibitors.";
RL Protein Sci. 3:118-125(1994).
RN [40]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF MUTANTS ARG-197; ASP-197 AND
RP PHE-197 IN COMPLEX WITH THE INHIBITOR ACETAZOLAMIDE.
RX PubMed=7696263; DOI=10.1021/bi00012a016;
RA Nair S.K., Krebs J.F., Christianson D.W., Fierke C.A.;
RT "Structural basis of inhibitor affinity to variants of human carbonic
RT anhydrase II.";
RL Biochemistry 34:3981-3989(1995).
RN [41]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) IN COMPLEX WITH INHIBITORS.
RX PubMed=7608893; DOI=10.1021/jm00013a004;
RA Boriack P.A., Christianson D.W., Kingery-Wood J., Whitesides G.M.;
RT "Secondary interactions significantly removed from the sulfonamide
RT binding pocket of carbonic anhydrase II influence inhibitor binding
RT constants.";
RL J. Med. Chem. 38:2286-2291(1995).
RN [42]
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF MUTANTS ASP-198; GLU-198 AND
RP HIS-198 IN COMPLEX WITH ZINC ION, MUTAGENESIS OF THR-198, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=7761440; DOI=10.1073/pnas.92.11.5017;
RA Ippolito J.A., Baird T.T. Jr., McGee S.A., Christianson D.W.,
RA Fierke C.A.;
RT "Structure-assisted redesign of a protein-zinc-binding site with
RT femtomolar affinity.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:5017-5021(1995).
RN [43]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF THE MUTANT GLN-117 IN
RP COMPLEX WITH ZINC ION AND THE INHIBITOR ACETAZOLAMIDE, AND MUTAGENESIS
RP OF GLU-117.
RX PubMed=8639494; DOI=10.1021/bi9526692;
RA Huang C.C., Lesburg C.A., Kiefer L.L., Fierke C.A., Christianson D.W.;
RT "Reversal of the hydrogen bond to zinc ligand histidine-119
RT dramatically diminishes catalysis and enhances metal equilibration
RT kinetics in carbonic anhydrase II.";
RL Biochemistry 35:3439-3446(1996).
RN [44]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF MUTANTS GLY-65; HIS-65;
RP LEU-65; PHE-65; SER-65 AND THR-65 IN COMPLEX WITH ZINC ION.
RX PubMed=8987974; DOI=10.1021/bi9617872;
RA Scolnick L.R., Christianson D.W.;
RT "X-ray crystallographic studies of alanine-65 variants of carbonic
RT anhydrase II reveal the structural basis of compromised proton
RT transfer in catalysis.";
RL Biochemistry 35:16429-16434(1996).
RN [45]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) IN COMPLEX WITH THE INHIBITOR
RP DANSYLAMIDE.
RX PubMed=8557623;
RA Nair S.K., Elbaum D., Christianson D.W.;
RT "Unexpected binding mode of the sulfonamide fluorophore 5-
RT dimethylamino-1-naphthalene sulfonamide to human carbonic anhydrase
RT II. Implications for the development of a zinc biosensor.";
RL J. Biol. Chem. 271:1003-1007(1996).
RN [46]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) IN COMPLEX WITH THE ACTIVATOR
RP HISTAMINE, AND ENZYME REGULATION.
RX PubMed=9265618; DOI=10.1021/bi970760v;
RA Briganti F., Mangani S., Orioli P., Scozzafava A., Vernaglione G.,
RA Supuran C.T.;
RT "Carbonic anhydrase activators: X-ray crystallographic and
RT spectroscopic investigations for the interaction of isozymes I and II
RT with histamine.";
RL Biochemistry 36:10384-10392(1997).
RN [47]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF MUTANTS ASN-94; ASN-119 AND
RP GLN-119 IN COMPLEX WITH ZINC ION, MUTAGENESIS OF HIS-94 AND HIS-119,
RP AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=9398308; DOI=10.1021/bi971296x;
RA Lesburg C.A., Huang C., Christianson D.W., Fierke C.A.;
RT "Histidine --> carboxamide ligand substitutions in the zinc binding
RT site of carbonic anhydrase II alter metal coordination geometry but
RT retain catalytic activity.";
RL Biochemistry 36:15780-15791(1997).
RN [48]
RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) IN COMPLEX WITH THE INHIBITOR
RP BRINZOLAMIDE.
RX PubMed=9541386;
RA Stams T., Chen Y., Boriack-Sjodin P.A., Hurt J.D., Liao J., May J.A.,
RA Dean T., Laipis P., Silverman D.N., Christianson D.W.;
RT "Structures of murine carbonic anhydrase IV and human carbonic
RT anhydrase II complexed with brinzolamide: molecular basis of isozyme-
RT drug discrimination.";
RL Protein Sci. 7:556-563(1998).
RN [49]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) IN COMPLEX WITH SULFONAMIDE
RP INHIBITORS AND ZINC ION.
RX PubMed=9865942; DOI=10.1002/pro.5560071201;
RA Boriack-Sjodin P.A., Zeitlin S., Chen H.H., Crenshaw L., Gross S.,
RA Dantanarayana A., Delgado P., May J.A., Dean T., Christianson D.W.;
RT "Structural analysis of inhibitor binding to human carbonic anhydrase
RT II.";
RL Protein Sci. 7:2483-2489(1998).
RN [50]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) IN COMPLEX WITH CYANAMIDE AND
RP SUBSTRATE, FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=10550681; DOI=10.1007/s007750050375;
RA Briganti F., Mangani S., Scozzafava A., Vernaglione G., Supuran C.T.;
RT "Carbonic anhydrase catalyzes cyanamide hydration to urea: is it
RT mimicking the physiological reaction?";
RL J. Biol. Inorg. Chem. 4:528-536(1999).
RN [51]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) IN COMPLEX WITH CYANAMIDE.
RX PubMed=11015219; DOI=10.1021/bi000937c;
RA Guerri A., Briganti F., Scozzafava A., Supuran C.T., Mangani S.;
RT "Mechanism of cyanamide hydration catalyzed by carbonic anhydrase II
RT suggested by cryogenic X-ray diffraction.";
RL Biochemistry 39:12391-12397(2000).
RN [52]
RP X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) OF MUTANTS ILE-93/MET-95/VAL-97
RP AND SER-93/LEU-95/MET-97 IN COMPLEX WITH COBALT; COPPER AND ZINC IONS.
RX PubMed=11076507; DOI=10.1021/bi001649j;
RA Cox J.D., Hunt J.A., Compher K.M., Fierke C.A., Christianson D.W.;
RT "Structural influence of hydrophobic core residues on metal binding
RT and specificity in carbonic anhydrase II.";
RL Biochemistry 39:13687-13694(2000).
RN [53]
RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF THE MUTANT ALA-64 IN COMPLEX
RP WITH 4-METHYLIMIDAZOLE, AND MUTAGENESIS OF HIS-64.
RX PubMed=11327835; DOI=10.1021/bi002295z;
RA Duda D., Tu C., Qian M., Laipis P., Agbandje-McKenna M.,
RA Silverman D.N., McKenna R.;
RT "Structural and kinetic analysis of the chemical rescue of the proton
RT transfer function of carbonic anhydrase II.";
RL Biochemistry 40:1741-1748(2001).
RN [54]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF MUTANT VAL-130 IN COMPLEX
RP WITH FLUOROAROMATIC INHIBITORS.
RX PubMed=11572683; DOI=10.1021/ja011034p;
RA Kim C.Y., Chandra P.P., Jain A., Christianson D.W.;
RT "Fluoroaromatic-fluoroaromatic interactions between inhibitors bound
RT in the crystal lattice of human carbonic anhydrase II.";
RL J. Am. Chem. Soc. 123:9620-9627(2001).
RN [55]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) IN COMPLEX WITH THE INHIBITOR
RP SUGAR SULFAMATE RWJ-37497, AND ENZYME REGULATION.
RX PubMed=11802772; DOI=10.1042/0264-6021:3610437;
RA Recacha R., Costanzo M.J., Maryanoff B.E., Chattopadhyay D.;
RT "Crystal structure of human carbonic anhydrase II complexed with an
RT anti-convulsant sugar sulphamate.";
RL Biochem. J. 361:437-441(2002).
RN [56]
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF THE MUTANT PRO-198/SER-205
RP IN COMPLEX WITH BICARBONATE AND INHIBITORS, AND MUTAGENESIS OF
RP THR-198.
RX PubMed=12056894; DOI=10.1021/bi020053o;
RA Huang S., Sjoeblom B., Sauer-Eriksson A.E., Jonsson B.H.;
RT "Organization of an efficient carbonic anhydrase: implications for the
RT mechanism based on structure-function studies of a T199P/C206S
RT mutant.";
RL Biochemistry 41:7628-7635(2002).
RN [57]
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF THE MUTANT HIS-7, AND
RP MUTAGENESIS OF TYR-7.
RX PubMed=12171926; DOI=10.1074/jbc.M205791200;
RA Tu C., Qian M., An H., Wadhwa N.R., Duda D., Yoshioka C., Pathak Y.,
RA McKenna R., Laipis P.J., Silverman D.N.;
RT "Kinetic analysis of multiple proton shuttles in the active site of
RT human carbonic anhydrase.";
RL J. Biol. Chem. 277:38870-38876(2002).
RN [58]
RP X-RAY CRYSTALLOGRAPHY (1.93 ANGSTROMS) IN COMPLEX WITH INHIBITORS, AND
RP FUNCTION.
RX PubMed=11831900; DOI=10.1021/jm010163d;
RA Kim C.Y., Whittington D.A., Chang J.S., Liao J., May J.A.,
RA Christianson D.W.;
RT "Structural aspects of isozyme selectivity in the binding of
RT inhibitors to carbonic anhydrases II and IV.";
RL J. Med. Chem. 45:888-893(2002).
RN [59]
RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) IN COMPLEX WITH INHIBITORS.
RX PubMed=12166932; DOI=10.1021/jm011112j;
RA Grueneberg S., Stubbs M.T., Klebe G.;
RT "Successful virtual screening for novel inhibitors of human carbonic
RT anhydrase: strategy and experimental confirmation.";
RL J. Med. Chem. 45:3588-3602(2002).
RN [60]
RP X-RAY CRYSTALLOGRAPHY (1.94 ANGSTROMS) IN COMPLEX WITH INHIBITORS.
RX PubMed=11818565; DOI=10.1073/pnas.032673399;
RA Grzybowski B.A., Ishchenko A.V., Kim C.Y., Topalov G., Chapman R.,
RA Christianson D.W., Whitesides G.M., Shakhnovich E.I.;
RT "Combinatorial computational method gives new picomolar ligands for a
RT known enzyme.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:1270-1273(2002).
RN [61]
RP X-RAY CRYSTALLOGRAPHY (1.05 ANGSTROMS) OF THE MUTANT ALA-64 IN COMPLEX
RP WITH THE INHIBITOR 4-METHYLIMIDAZOLE AND ZINC ION.
RX PubMed=12499545;
RA Duda D., Govindasamy L., Agbandje-McKenna M., Tu C., Silverman D.N.,
RA McKenna R.;
RT "The refined atomic structure of carbonic anhydrase II at 1.05 A
RT resolution: implications of chemical rescue of proton transfer.";
RL Acta Crystallogr. D 59:93-104(2003).
RN [62]
RP X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) IN COMPLEX WITH INHIBITORS, AND
RP ENZYME REGULATION.
RX PubMed=14736236; DOI=10.1021/jm030912m;
RA Weber A., Casini A., Heine A., Kuhn D., Supuran C.T., Scozzafava A.,
RA Klebe G.;
RT "Unexpected nanomolar inhibition of carbonic anhydrase by COX-2-
RT selective celecoxib: new pharmacological opportunities due to related
RT binding site recognition.";
RL J. Med. Chem. 47:550-557(2004).
RN [63]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) IN COMPLEX WITH THE ANTI-CANCER
RP AGENT 667-COUMATE.
RX PubMed=15453828; DOI=10.1042/BJ20041037;
RA Lloyd M.D., Pederick R.L., Natesh R., Woo L.W., Purohit A., Reed M.J.,
RA Acharya K.R., Potter B.V.;
RT "Crystal structure of human carbonic anhydrase II at 1.95 A resolution
RT in complex with 667-coumate, a novel anti-cancer agent.";
RL Biochem. J. 385:715-720(2005).
RN [64]
RP X-RAY CRYSTALLOGRAPHY (1.63 ANGSTROMS), MUTAGENESIS OF ASN-62; HIS-64
RP AND ASN-67, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=15667203; DOI=10.1021/bi0480279;
RA Fisher Z., Hernandez Prada J.A., Tu C., Duda D., Yoshioka C., An H.,
RA Govindasamy L., Silverman D.N., McKenna R.;
RT "Structural and kinetic characterization of active-site histidine as a
RT proton shuttle in catalysis by human carbonic anhydrase II.";
RL Biochemistry 44:1097-1105(2005).
RN [65]
RP X-RAY CRYSTALLOGRAPHY (1.76 ANGSTROMS) IN COMPLEX WITH DUAL
RP AROMATASE-STEROID SULFATASE INHIBITORS.
RX PubMed=15865431; DOI=10.1021/bi047692e;
RA Lloyd M.D., Thiyagarajan N., Ho Y.T., Woo L.W., Sutcliffe O.B.,
RA Purohit A., Reed M.J., Acharya K.R., Potter B.V.;
RT "First crystal structures of human carbonic anhydrase II in complex
RT with dual aromatase-steroid sulfatase inhibitors.";
RL Biochemistry 44:6858-6866(2005).
RN [66]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) IN COMPLEX WITH ACTIVATOR
RP L-HISTIDINE, AND ENZYME REGULATION.
RX PubMed=16214338; DOI=10.1016/j.bmcl.2005.08.069;
RA Temperini C., Scozzafava A., Puccetti L., Supuran C.T.;
RT "Carbonic anhydrase activators: X-ray crystal structure of the adduct
RT of human isozyme II with L-histidine as a platform for the design of
RT stronger activators.";
RL Bioorg. Med. Chem. Lett. 15:5136-5141(2005).
RN [67]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) IN COMPLEX WITH INHIBITOR.
RX PubMed=16134940; DOI=10.1021/jm050333c;
RA Menchise V., De Simone G., Alterio V., Di Fiore A., Pedone C.,
RA Scozzafava A., Supuran C.T.;
RT "Carbonic anhydrase inhibitors: stacking with Phe131 determines active
RT site binding region of inhibitors as exemplified by the X-ray crystal
RT structure of a membrane-impermeant antitumor sulfonamide complexed
RT with isozyme II.";
RL J. Med. Chem. 48:5721-5727(2005).
RN [68]
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS), AND MUTAGENESIS OF HIS-64 AND
RP THR-199.
RX PubMed=16106378; DOI=10.1002/prot.20615;
RA Bhatt D., Tu C., Fisher S.Z., Hernandez Prada J.A., McKenna R.,
RA Silverman D.N.;
RT "Proton transfer in a Thr200His mutant of human carbonic anhydrase
RT II.";
RL Proteins 61:239-245(2005).
RN [69]
RP X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS).
RX PubMed=16511248; DOI=10.1107/S1744309105038248;
RA Budayova-Spano M., Fisher S.Z., Dauvergne M.T., Agbandje-McKenna M.,
RA Silverman D.N., Myles D.A., McKenna R.;
RT "Production and X-ray crystallographic analysis of fully deuterated
RT human carbonic anhydrase II.";
RL Acta Crystallogr. F 62:6-9(2006).
RN [70]
RP X-RAY CRYSTALLOGRAPHY (1.15 ANGSTROMS) IN COMPLEX WITH INHIBITORS.
RX PubMed=16820676; DOI=10.1107/S1744309106020446;
RA Fisher S.Z., Govindasamy L., Boyle N., Agbandje-McKenna M.,
RA Silverman D.N., Blackburn G.M., McKenna R.;
RT "X-ray crystallographic studies reveal that the incorporation of
RT spacer groups in carbonic anhydrase inhibitors causes alternate
RT binding modes.";
RL Acta Crystallogr. F 62:618-622(2006).
RN [71]
RP X-RAY CRYSTALLOGRAPHY (1.46 ANGSTROMS) IN COMPLEX WITH INHIBITORS
RP VALDECOXIB AND CELECOXIB, AND ENZYME REGULATION.
RX PubMed=16290146; DOI=10.1016/j.bmcl.2005.09.040;
RA Di Fiore A., Pedone C., D'Ambrosio K., Scozzafava A., De Simone G.,
RA Supuran C.T.;
RT "Carbonic anhydrase inhibitors: Valdecoxib binds to a different active
RT site region of the human isoform II as compared to the structurally
RT related cyclooxygenase II 'selective' inhibitor celecoxib.";
RL Bioorg. Med. Chem. Lett. 16:437-442(2006).
RN [72]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) IN COMPLEX WITH N-HYDROXYUREA,
RP AND ENZYME REGULATION.
RX PubMed=16759856; DOI=10.1016/j.bmcl.2006.05.068;
RA Temperini C., Innocenti A., Scozzafava A., Supuran C.T.;
RT "N-hydroxyurea -- a versatile zinc binding function in the design of
RT metalloenzyme inhibitors.";
RL Bioorg. Med. Chem. Lett. 16:4316-4320(2006).
RN [73]
RP X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) IN COMPLEX WITH INHIBITORS.
RX PubMed=17000110; DOI=10.1016/j.bmcl.2006.09.022;
RA Menchise V., De Simone G., Di Fiore A., Scozzafava A., Supuran C.T.;
RT "Carbonic anhydrase inhibitors: X-ray crystallographic studies for the
RT binding of 5-amino-1,3,4-thiadiazole-2-sulfonamide and 5-(4-amino-3-
RT chloro-5-fluorophenylsulfonamido)-1,3,4-thiadiazole-2-sulfonamide to
RT human isoform II.";
RL Bioorg. Med. Chem. Lett. 16:6204-6208(2006).
RN [74]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) IN COMPLEX WITH L- AND
RP D-HISTIDINE, AND ENZYME REGULATION.
RX PubMed=16807956; DOI=10.1002/chem.200600159;
RA Temperini C., Scozzafava A., Vullo D., Supuran C.T.;
RT "Carbonic anhydrase activators. Activation of isozymes I, II, IV, VA,
RT VII, and XIV with l- and d-histidine and crystallographic analysis of
RT their adducts with isoform II: engineering proton-transfer processes
RT within the active site of an enzyme.";
RL Chemistry 12:7057-7066(2006).
RN [75]
RP X-RAY CRYSTALLOGRAPHY (0.99 ANGSTROMS) IN COMPLEX WITH TWO-PRONG
RP INHIBITORS.
RX PubMed=16506782; DOI=10.1021/ja057257n;
RA Jude K.M., Banerjee A.L., Haldar M.K., Manokaran S., Roy B.,
RA Mallik S., Srivastava D.K., Christianson D.W.;
RT "Ultrahigh resolution crystal structures of human carbonic anhydrases
RT I and II complexed with 'two-prong' inhibitors reveal the molecular
RT basis of high affinity.";
RL J. Am. Chem. Soc. 128:3011-3018(2006).
RN [76]
RP X-RAY CRYSTALLOGRAPHY (1.71 ANGSTROMS) IN COMPLEX WITH INHIBITOR.
RX PubMed=16787097; DOI=10.1021/ja061574s;
RA Alterio V., Vitale R.M., Monti S.M., Pedone C., Scozzafava A.,
RA Cecchi A., De Simone G., Supuran C.T.;
RT "Carbonic anhydrase inhibitors: X-ray and molecular modeling study for
RT the interaction of a fluorescent antitumor sulfonamide with isozyme II
RT and IX.";
RL J. Am. Chem. Soc. 128:8329-8335(2006).
RN [77]
RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) IN COMPLEX WITH L- AND
RP D-PHENYLALANINE, AND ENZYME REGULATION.
RX PubMed=16686544; DOI=10.1021/jm0603320;
RA Temperini C., Scozzafava A., Vullo D., Supuran C.T.;
RT "Carbonic anhydrase activators. Activation of isoforms I, II, IV, VA,
RT VII, and XIV with L- and D-phenylalanine and crystallographic analysis
RT of their adducts with isozyme II: stereospecific recognition within
RT the active site of an enzyme and its consequences for the drug
RT design.";
RL J. Med. Chem. 49:3019-3027(2006).
RN [78]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) IN COMPLEX WITH INHIBITOR.
RX PubMed=16942027; DOI=10.1021/jm060531j;
RA De Simone G., Vitale R.M., Di Fiore A., Pedone C., Scozzafava A.,
RA Montero J.-L., Winum J.-Y., Supuran C.T.;
RT "Carbonic anhydrase inhibitors: Hypoxia-activatable sulfonamides
RT incorporating disulfide bonds that target the tumor-associated isoform
RT IX.";
RL J. Med. Chem. 49:5544-5551(2006).
RN [79]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) IN COMPLEX WITH INHIBITOR.
RX PubMed=17125255; DOI=10.1021/jm060807n;
RA Winum J.Y., Temperini C., El Cheikh K., Innocenti A., Vullo D.,
RA Ciattini S., Montero J.-L., Scozzafava A., Supuran C.T.;
RT "Carbonic anhydrase inhibitors: clash with Ala65 as a means for
RT designing inhibitors with low affinity for the ubiquitous isozyme II,
RT exemplified by the crystal structure of the topiramate sulfamide
RT analogue.";
RL J. Med. Chem. 49:7024-7031(2006).
RN [80]
RP X-RAY CRYSTALLOGRAPHY (1.46 ANGSTROMS) IN COMPLEX WITH INHIBITORS.
RX PubMed=17181151; DOI=10.1021/jm060705x;
RA Leese M.P., Leblond B., Smith A., Newman S.P., Di Fiore A.,
RA De Simone G., Supuran C.T., Purohit A., Reed M.J., Potter B.V.;
RT "2-substituted estradiol bis-sulfamates, multitargeted antitumor
RT agents: synthesis, in vitro SAR, protein crystallography, and in vivo
RT activity.";
RL J. Med. Chem. 49:7683-7696(2006).
RN [81]
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) IN COMPLEX WITH SACCHARIN, AND
RP ENZYME REGULATION.
RX PubMed=17705204; DOI=10.1002/anie.200701189;
RA Koehler K., Hillebrecht A., Schulze Wischeler J., Innocenti A.,
RA Heine A., Supuran C.T., Klebe G.;
RT "Saccharin inhibits carbonic anhydrases: possible explanation for its
RT unpleasant metallic aftertaste.";
RL Angew. Chem. Int. Ed. Engl. 46:7697-7699(2007).
RN [82]
RP X-RAY CRYSTALLOGRAPHY (1.05 ANGSTROMS).
RX PubMed=17319692; DOI=10.1021/bi062066y;
RA Fisher S.Z., Maupin C.M., Budayova-Spano M., Govindasamy L., Tu C.,
RA Agbandje-McKenna M., Silverman D.N., Voth G.A., McKenna R.;
RT "Atomic crystal and molecular dynamics simulation structures of human
RT carbonic anhydrase II: insights into the proton transfer mechanism.";
RL Biochemistry 46:2930-2937(2007).
RN [83]
RP X-RAY CRYSTALLOGRAPHY (1.15 ANGSTROMS), MUTAGENESIS OF TYR-7; ASN-62
RP AND ASN-67, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=17330962; DOI=10.1021/bi602620k;
RA Fisher S.Z., Tu C., Bhatt D., Govindasamy L., Agbandje-McKenna M.,
RA McKenna R., Silverman D.N.;
RT "Speeding up proton transfer in a fast enzyme: kinetic and
RT crystallographic studies on the effect of hydrophobic amino acid
RT substitutions in the active site of human carbonic anhydrase II.";
RL Biochemistry 46:3803-3813(2007).
RN [84]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) IN COMPLEX WITH ACTIVATOR
RP L-ADRENALINE, AND ENZYME REGULATION.
RX PubMed=17127057; DOI=10.1016/j.bmcl.2006.11.027;
RA Temperini C., Innocenti A., Scozzafava A., Mastrolorenzo A.,
RA Supuran C.T.;
RT "Carbonic anhydrase activators: L-Adrenaline plugs the active site
RT entrance of isozyme II, activating better isoforms I, IV, VA, VII, and
RT XIV.";
RL Bioorg. Med. Chem. Lett. 17:628-635(2007).
RN [85]
RP X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) IN COMPLEX WITH INHIBITOR.
RX PubMed=17251017; DOI=10.1016/j.bmcl.2006.12.099;
RA Di Fiore A., Scozzafava A., Winum J.-Y., Montero J.-L., Pedone C.,
RA Supuran C.T., De Simone G.;
RT "Carbonic anhydrase inhibitors: binding of an antiglaucoma glycosyl-
RT sulfanilamide derivative to human isoform II and its consequences for
RT the drug design of enzyme inhibitors incorporating sugar moieties.";
RL Bioorg. Med. Chem. Lett. 17:1726-1731(2007).
RN [86]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) IN COMPLEX WITH INHIBITOR
RP N-HYDROXYSULFAMIDE.
RX PubMed=17346964; DOI=10.1016/j.bmcl.2007.02.068;
RA Temperini C., Winum J.Y., Montero J.L., Scozzafava A., Supuran C.T.;
RT "Carbonic anhydrase inhibitors: the X-ray crystal structure of the
RT adduct of N-hydroxysulfamide with isozyme II explains why this new
RT zinc binding function is effective in the design of potent
RT inhibitors.";
RL Bioorg. Med. Chem. Lett. 17:2795-2801(2007).
RN [87]
RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) IN COMPLEX WITH INHIBITORS, AND
RP ENZYME REGULATION.
RX PubMed=17540563; DOI=10.1016/j.bmcl.2007.05.045;
RA Alterio V., De Simone G., Monti S.M., Scozzafava A., Supuran C.T.;
RT "Carbonic anhydrase inhibitors: inhibition of human, bacterial, and
RT archaeal isozymes with benzene-1,3-disulfonamides -- solution and
RT crystallographic studies.";
RL Bioorg. Med. Chem. Lett. 17:4201-4207(2007).
RN [88]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) IN COMPLEX WITH INHIBITORS, AND
RP ENZYME REGULATION.
RX PubMed=17588751; DOI=10.1016/j.bmcl.2007.06.044;
RA Temperini C., Innocenti A., Mastrolorenzo A., Scozzafava A.,
RA Supuran C.T.;
RT "Carbonic anhydrase inhibitors. Interaction of the antiepileptic drug
RT sulthiame with twelve mammalian isoforms: kinetic and X-ray
RT crystallographic studies.";
RL Bioorg. Med. Chem. Lett. 17:4866-4872(2007).
RN [89]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) IN COMPLEX WITH
RP 4-METHYLIMIDAZOLE, AND MUTAGENESIS OF TRP-5 AND HIS-64.
RX PubMed=17071654; DOI=10.1529/biophysj.106.093203;
RA Bhatt D., Fisher S.Z., Tu C., McKenna R., Silverman D.N.;
RT "Location of binding sites in small molecule rescue of human carbonic
RT anhydrase II.";
RL Biophys. J. 92:562-570(2007).
RN [90]
RP X-RAY CRYSTALLOGRAPHY (1.01 ANGSTROMS) IN COMPLEX WITH INHIBITORS.
RX PubMed=17407288; DOI=10.1021/ja068359w;
RA Srivastava D.K., Jude K.M., Banerjee A.L., Haldar M., Manokaran S.,
RA Kooren J., Mallik S., Christianson D.W.;
RT "Structural analysis of charge discrimination in the binding of
RT inhibitors to human carbonic anhydrases I and II.";
RL J. Am. Chem. Soc. 129:5528-5537(2007).
RN [91]
RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) IN COMPLEX WITH INHIBITOR
RP THIOXOLONE, AND ENZYME REGULATION.
RX PubMed=18266323; DOI=10.1021/bi702385k;
RA Barrese A.A. III, Genis C., Fisher S.Z., Orwenyo J.N., Kumara M.T.,
RA Dutta S.K., Phillips E., Kiddle J.J., Tu C., Silverman D.N.,
RA Govindasamy L., Agbandje-McKenna M., McKenna R., Tripp B.C.;
RT "Inhibition of carbonic anhydrase II by thioxolone: a mechanistic and
RT structural study.";
RL Biochemistry 47:3174-3184(2008).
RN [92]
RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF MUTANTS, MUTAGENESIS OF
RP ASN-62, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=18942852; DOI=10.1021/bi801473w;
RA Zheng J., Avvaru B.S., Tu C., McKenna R., Silverman D.N.;
RT "Role of hydrophilic residues in proton transfer during catalysis by
RT human carbonic anhydrase II.";
RL Biochemistry 47:12028-12036(2008).
RN [93]
RP X-RAY CRYSTALLOGRAPHY (1.89 ANGSTROMS) IN COMPLEX WITH INHIBITORS, AND
RP ENZYME REGULATION.
RX PubMed=18024029; DOI=10.1016/j.bmcl.2007.10.110;
RA Guezel O., Temperini C., Innocenti A., Scozzafava A., Salman A.,
RA Supuran C.T.;
RT "Carbonic anhydrase inhibitors. Interaction of 2-(hydrazinocarbonyl)-
RT 3-phenyl-1H-indole-5-sulfonamide with 12 mammalian isoforms: kinetic
RT and X-ray crystallographic studies.";
RL Bioorg. Med. Chem. Lett. 18:152-158(2008).
RN [94]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) IN COMPLEX WITH INHIBITORS, AND
RP ENZYME REGULATION.
RX PubMed=18162396; DOI=10.1016/j.bmcl.2007.12.022;
RA Temperini C., Cecchi A., Boyle N.A., Scozzafava A., Cabeza J.E.,
RA Wentworth P. Jr., Blackburn G.M., Supuran C.T.;
RT "Carbonic anhydrase inhibitors. Interaction of 2-N,N-dimethylamino-
RT 1,3,4-thiadiazole-5-methanesulfonamide with 12 mammalian isoforms:
RT kinetic and X-ray crystallographic studies.";
RL Bioorg. Med. Chem. Lett. 18:999-1005(2008).
RN [95]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) IN COMPLEX WITH INHIBITORS, AND
RP ENZYME REGULATION.
RX PubMed=18374572; DOI=10.1016/j.bmcl.2008.03.051;
RA Temperini C., Cecchi A., Scozzafava A., Supuran C.T.;
RT "Carbonic anhydrase inhibitors. Interaction of indapamide and related
RT diuretics with 12 mammalian isozymes and X-ray crystallographic
RT studies for the indapamide-isozyme II adduct.";
RL Bioorg. Med. Chem. Lett. 18:2567-2573(2008).
RN [96]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) IN COMPLEX WITH INHIBITORS.
RX PubMed=18359629; DOI=10.1016/j.bmcl.2008.03.023;
RA Di Fiore A., Pedone C., Antel J., Waldeck H., Witte A., Wurl M.,
RA Scozzafava A., Supuran C.T., De Simone G.;
RT "Carbonic anhydrase inhibitors: the X-ray crystal structure of
RT ethoxzolamide complexed to human isoform II reveals the importance of
RT thr200 and gln92 for obtaining tight-binding inhibitors.";
RL Bioorg. Med. Chem. Lett. 18:2669-2674(2008).
RN [97]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) IN COMPLEX WITH INHIBITORS, AND
RP ENZYME REGULATION.
RX PubMed=18640037; DOI=10.1016/j.bmcl.2008.06.105;
RA Temperini C., Innocenti A., Scozzafava A., Supuran C.T.;
RT "Carbonic anhydrase inhibitors. Interaction of the antitumor sulfamate
RT EMD 486019 with twelve mammalian carbonic anhydrase isoforms: Kinetic
RT and X-ray crystallographic studies.";
RL Bioorg. Med. Chem. Lett. 18:4282-4286(2008).
RN [98]
RP X-RAY CRYSTALLOGRAPHY (1.40 ANGSTROMS) IN COMPLEX WITH INHIBITORS
RP INDANESULFONAMIDES.
RX PubMed=18161740; DOI=10.1002/cmdc.200700274;
RA D'Ambrosio K., Masereel B., Thiry A., Scozzafava A., Supuran C.T.,
RA De Simone G.;
RT "Carbonic anhydrase inhibitors: binding of indanesulfonamides to the
RT human isoform II.";
RL ChemMedChem 3:473-477(2008).
RN [99]
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) IN COMPLEX WITH
RP (129)XE-CRYPTOPHANE BIOSENSOR.
RX PubMed=18461940; DOI=10.1021/ja802214x;
RA Aaron J.A., Chambers J.M., Jude K.M., Di Costanzo L., Dmochowski I.J.,
RA Christianson D.W.;
RT "Structure of a (129)Xe-cryptophane biosensor complexed with human
RT carbonic anhydrase II.";
RL J. Am. Chem. Soc. 130:6942-6943(2008).
RN [100]
RP X-RAY CRYSTALLOGRAPHY (1.10 ANGSTROMS) IN COMPLEX WITH CO2.
RX PubMed=18768466; DOI=10.1074/jbc.M805353200;
RA Domsic J.F., Avvaru B.S., Kim C.U., Gruner S.M., Agbandje-McKenna M.,
RA Silverman D.N., McKenna R.;
RT "Entrapment of carbon dioxide in the active site of carbonic anhydrase
RT II.";
RL J. Biol. Chem. 283:30766-30771(2008).
RN [101]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) IN COMPLEX WITH INHIBITORS.
RX PubMed=18260615; DOI=10.1021/jm701319c;
RA Leese M.P., Jourdan F.L., Gaukroger K., Mahon M.F., Newman S.P.,
RA Foster P.A., Stengel C., Regis-Lydi S., Ferrandis E., Di Fiore A.,
RA De Simone G., Supuran C.T., Purohit A., Reed M.J., Potter B.V.;
RT "Structure-activity relationships of C-17 cyano-substituted
RT estratrienes as anticancer agents.";
RL J. Med. Chem. 51:1295-1308(2008).
RN [102]
RP X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) IN COMPLEX WITH INHIBITORS, AND
RP ENZYME REGULATION.
RX PubMed=18481843; DOI=10.1021/jm800121c;
RA D'Ambrosio K., Vitale R.-M., Dogne J.-M., Masereel B., Innocenti A.,
RA Scozzafava A., De Simone G., Supuran C.T.;
RT "Carbonic anhydrase inhibitors: bioreductive nitro-containing
RT sulfonamides with selectivity for targeting the tumor associated
RT isoforms IX and XII.";
RL J. Med. Chem. 51:3230-3237(2008).
RN [103]
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) IN COMPLEX WITH INHIBITORS.
RX PubMed=18723489; DOI=10.1158/1535-7163.MCT-08-0195;
RA Woo L.W.L., Fischer D.S., Sharland C.M., Trusselle M., Foster P.A.,
RA Chander S.K., Di Fiore A., Supuran C.T., De Simone G., Purohit A.,
RA Reed M.J., Potter B.V.L.;
RT "Anticancer steroid sulfatase inhibitors: synthesis of a potent
RT fluorinated second-generation agent, in vitro and in vivo activities,
RT molecular modeling, and protein crystallography.";
RL Mol. Cancer Ther. 7:2435-2444(2008).
RN [104]
RP X-RAY CRYSTALLOGRAPHY (1.48 ANGSTROMS) IN COMPLEX WITH INHIBITORS,
RP ENZYME REGULATION, AND MUTAGENESIS OF ALA-65 AND ASN-67.
RX PubMed=19170619; DOI=10.1021/bi802035f;
RA Genis C., Sippel K.H., Case N., Cao W., Avvaru B.S., Tartaglia L.J.,
RA Govindasamy L., Tu C., Agbandje-McKenna M., Silverman D.N.,
RA Rosser C.J., McKenna R.;
RT "Design of a carbonic anhydrase IX active-site mimic to screen
RT inhibitors for possible anticancer properties.";
RL Biochemistry 48:1322-1331(2009).
RN [105]
RP X-RAY CRYSTALLOGRAPHY (1.26 ANGSTROMS) FREE AND IN COMPLEX WITH ZINC
RP ION, AND COFACTOR.
RX PubMed=19583303; DOI=10.1021/bi9007512;
RA Avvaru B.S., Busby S.A., Chalmers M.J., Griffin P.R.,
RA Venkatakrishnan B., Agbandje-McKenna M., Silverman D.N., McKenna R.;
RT "Apo-human carbonic anhydrase II revisited: implications of the loss
RT of a metal in protein structure, stability, and solvent network.";
RL Biochemistry 48:7365-7372(2009).
RN [106]
RP X-RAY CRYSTALLOGRAPHY (1.81 ANGSTROMS) OF 1-260 IN COMPLEX WITH
RP INHIBITOR THIABENDAZOLE-5-SULFONAMIDE, AND ENZYME REGULATION.
RX PubMed=19186056; DOI=10.1016/j.bmcl.2009.01.038;
RA Crocetti L., Maresca A., Temperini C., Hall R.A., Scozzafava A.,
RA Muehlschlegel F.A., Supuran C.T.;
RT "A thiabendazole sulfonamide shows potent inhibitory activity against
RT mammalian and nematode alpha-carbonic anhydrases.";
RL Bioorg. Med. Chem. Lett. 19:1371-1375(2009).
RN [107]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 1-260 IN COMPLEX WITH
RP COUMARIN INHIBITORS, AND ENZYME REGULATION.
RX PubMed=19206230; DOI=10.1021/ja809683v;
RA Maresca A., Temperini C., Vu H., Pham N.B., Poulsen S.-A.,
RA Scozzafava A., Quinn R.J., Supuran C.T.;
RT "Non-zinc mediated inhibition of carbonic anhydrases: coumarins are a
RT new class of suicide inhibitors.";
RL J. Am. Chem. Soc. 131:3057-3062(2009).
RN [108]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) IN COMPLEX WITH INHIBITORS.
RX PubMed=19115843; DOI=10.1021/jm801386n;
RA Temperini C., Cecchi A., Scozzafava A., Supuran C.T.;
RT "Carbonic anhydrase inhibitors. Comparison of chlorthalidone and
RT indapamide X-ray crystal structures in adducts with isozyme II: when
RT three water molecules and the keto-enol tautomerism make the
RT difference.";
RL J. Med. Chem. 52:322-328(2009).
RN [109]
RP X-RAY CRYSTALLOGRAPHY (1.41 ANGSTROMS) IN COMPLEX WITH INHIBITORS.
RX PubMed=19731956; DOI=10.1021/jm900641r;
RA Vitale R.M., Alterio V., Innocenti A., Winum J.-Y., Monti S.M.,
RA De Simone G., Supuran C.T.;
RT "Carbonic anhydrase inhibitors. Comparison of aliphatic sulfamate/bis-
RT sulfamate adducts with isozymes II and IX as a platform for designing
RT tight-binding, more isoform-selective inhibitors.";
RL J. Med. Chem. 52:5990-5998(2009).
RN [110]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 1-260 IN COMPLEX WITH
RP INHIBITORS.
RX PubMed=19827837; DOI=10.1021/jm900914e;
RA Lopez M., Paul B., Hofmann A., Morizzi J., Wu Q.K., Charman S.A.,
RA Innocenti A., Vullo D., Supuran C.T., Poulsen S.-A.;
RT "S-glycosyl primary sulfonamides--a new structural class for selective
RT inhibition of cancer-associated carbonic anhydrases.";
RL J. Med. Chem. 52:6421-6432(2009).
RN [111]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 1-260 IN COMPLEX WITH
RP INHIBITORS, AND ENZYME REGULATION.
RX PubMed=19778001; DOI=10.1021/jp906593c;
RA Ciani L., Cecchi A., Temperini C., Supuran C.T., Ristori S.;
RT "Dissecting the inhibition mechanism of cytosolic versus transmembrane
RT carbonic anhydrases by ESR.";
RL J. Phys. Chem. B 113:13998-14005(2009).
RN [112]
RP X-RAY CRYSTALLOGRAPHY (1.56 ANGSTROMS) IN COMPLEX WITH SUBSTRATES, AND
RP ENZYME REGULATION.
RX PubMed=19520834; DOI=10.1073/pnas.0904184106;
RA Sjoeblom B., Polentarutti M., Djinovic-Carugo K.;
RT "Structural study of X-ray induced activation of carbonic anhydrase.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:10609-10613(2009).
RN [113]
RP VARIANT JOGJAKARTA GLU-18.
RX PubMed=6817747; DOI=10.1007/BF00484072;
RA Jones G.L., Sofro A.S.M., Shaw D.C.;
RT "Chemical and enzymological characterization of an Indonesian variant
RT of human erythrocyte carbonic anhydrase II, CAII Jogjakarta (17 Lys
RT leads to Glu).";
RL Biochem. Genet. 20:979-1000(1982).
RN [114]
RP VARIANT MELBOURNE HIS-236.
RX PubMed=6407977; DOI=10.1007/BF00274768;
RA Jones G.L., Shaw D.C.;
RT "A chemical and enzymological comparison of the common major human
RT erythrocyte carbonic anhydrase II, its minor component, and a new
RT genetic variant, CA II Melbourne (237 Pro leads to His).";
RL Hum. Genet. 63:392-399(1983).
RN [115]
RP VARIANT OPTB3 TYR-107.
RX PubMed=1928091;
RA Venta P.J., Welty R.J., Johnson T.M., Sly W.S., Tashian R.E.;
RT "Carbonic anhydrase II deficiency syndrome in a Belgian family is
RT caused by a point mutation at an invariant histidine residue (107
RT His-->Tyr): complete structure of the normal human CA II gene.";
RL Am. J. Hum. Genet. 49:1082-1090(1991).
RN [116]
RP VARIANT OPTB3 TYR-107.
RX PubMed=1542674; DOI=10.1073/pnas.89.5.1804;
RA Roth D.E., Venta P.J., Tashian R.E., Sly W.S.;
RT "Molecular basis of human carbonic anhydrase II deficiency.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:1804-1808(1992).
RN [117]
RP VARIANT OPTB3 TYR-107.
RX PubMed=8834238; DOI=10.1007/s004390050068;
RA Soda H., Yukizane S., Yoshida I., Koga Y., Aramaki S., Kato H.;
RT "A point mutation in exon 3 (His 107-->Tyr) in two unrelated Japanese
RT patients with carbonic anhydrase II deficiency with central nervous
RT system involvement.";
RL Hum. Genet. 97:435-437(1996).
RN [118]
RP VARIANT OPTB3 PRO-92.
RX PubMed=9143915;
RX DOI=10.1002/(SICI)1098-1004(1997)9:5<383::AID-HUMU1>3.3.CO;2-K;
RA Hu P.Y., Lim E.J., Ciccolella J., Strisciuglio P., Sly W.S.;
RT "Seven novel mutations in carbonic anhydrase II deficiency syndrome
RT identified by SSCP and direct sequencing analysis.";
RL Hum. Mutat. 9:383-387(1997).
RN [119]
RP VARIANTS OPTB3 PRO-92; TYR-94; TYR-107 AND ARG-144, AND
RP CHARACTERIZATION OF VARIANTS TYR-94 AND ARG-144.
RX PubMed=15300855; DOI=10.1002/humu.9266;
RA Shah G.N., Bonapace G., Hu P.Y., Strisciuglio P., Sly W.S.;
RT "Carbonic anhydrase II deficiency syndrome (osteopetrosis with renal
RT tubular acidosis and brain calcification): novel mutations in CA2
RT identified by direct sequencing expand the opportunity for genotype-
RT phenotype correlation.";
RL Hum. Mutat. 24:272-272(2004).
CC -!- FUNCTION: Essential for bone resorption and osteoclast
CC differentiation (By similarity). Reversible hydration of carbon
CC dioxide. Can hydrate cyanamide to urea. Involved in the regulation
CC of fluid secretion into the anterior chamber of the eye.
CC Contributes to intracellular pH regulation in the duodenal upper
CC villous epithelium during proton-coupled peptide absorption.
CC Stimulates the chloride-bicarbonate exchange activity of SLC26A6.
CC -!- CATALYTIC ACTIVITY: H(2)CO(3) = CO(2) + H(2)O.
CC -!- COFACTOR: Zinc. Can also use cobalt(II) with lower efficiency, but
CC not copper(II), nickel(II) and manganese(II).
CC -!- ENZYME REGULATION: Activated by X-ray, histamine, L-adrenaline, L-
CC and D-phenylalanine, L- and D-histidine, L-His-OMe and beta-Ala-
CC His (carnosine). Competitively inhibited by saccharin, thioxolone,
CC coumarins, 667-coumate, celecoxib (Celebrex), valdecoxib (Bextra),
CC SC-125, SC-560, diclofenac, acetate, azide, bromide, sulfonamide
CC derivatives such as acetazolamide (AZA), methazolamide (MZA),
CC ethoxzolamide (EZA), dichlorophenamide (DCP), brinzolamide,
CC dansylamide, thiabendazole-5-sulfonamide, trifluoromethane
CC sulfonamide and N-hydroxysulfamide, fructose-based sugar sulfamate
CC RWJ-37497, and Foscarnet (phosphonoformate trisodium salt).
CC Repressed strongly by hydrogen sulfide(HS) and weakly by nitrate
CC (NO(3)). Esterase activity weakly reduced by cyanamide. N-
CC hydroxyurea interfers with zinc binding and inhibit activity.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Absorption:
CC Abs(max)=550 nm;
CC Note=At pH 7.0. Shows a second maximum at 618 nm;
CC Kinetic parameters:
CC KM=10 mM for CO(2);
CC KM=82 mM for H(2)CO(3);
CC KM=3 mM for 4-nitrophenyl acetate;
CC pH dependence:
CC Optimum pH is 6-8;
CC -!- SUBUNIT: Interacts with SLC4A4. Interaction with SLC4A7 regulates
CC SLC4A7 transporter activity. Interacts with SLC26A6 isoform 4 (via
CC C-terminus cytoplasmic domain).
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cell membrane. Note=Colocalized
CC with SLC26A6 at the surface of the cell membrane in order to form
CC a bicarbonate transport metabolon. Displaced from the cytosolic
CC surface of the cell membrane by PKC in phorbol myristate acetate
CC (PMA)-induced cells.
CC -!- DISEASE: Osteopetrosis, autosomal recessive 3 (OPTB3)
CC [MIM:259730]: A rare genetic disease characterized by abnormally
CC dense bone, due to defective resorption of immature bone.
CC Osteopetrosis occurs in two forms: a severe autosomal recessive
CC form occurring in utero, infancy, or childhood, and a benign
CC autosomal dominant form occurring in adolescence or adulthood.
CC Recessive osteopetrosis commonly manifests in early infancy with
CC macrocephaly, feeding difficulties, evolving blindness and
CC deafness, bone marrow failure, severe anemia, and
CC hepatosplenomegaly. Deafness and blindness are generally thought
CC to represent effects of pressure on nerves. OPTB3 is associated
CC with renal tubular acidosis, cerebral calcification (marble brain
CC disease) and in some cases with mental retardation. Note=The
CC disease is caused by mutations affecting the gene represented in
CC this entry.
CC -!- MISCELLANEOUS: Target of drugs used in treatments against glaucoma
CC disorder and breast cancer.
CC -!- SIMILARITY: Belongs to the alpha-carbonic anhydrase family.
CC -!- WEB RESOURCE: Name=GeneReviews;
CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/CA2";
CC -----------------------------------------------------------------------
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DR EMBL; M77181; AAA51909.1; -; Genomic_DNA.
DR EMBL; M77176; AAA51909.1; JOINED; Genomic_DNA.
DR EMBL; M77177; AAA51909.1; JOINED; Genomic_DNA.
DR EMBL; M77178; AAA51909.1; JOINED; Genomic_DNA.
DR EMBL; M77179; AAA51909.1; JOINED; Genomic_DNA.
DR EMBL; M77180; AAA51909.1; JOINED; Genomic_DNA.
DR EMBL; Y00339; CAA68426.1; -; mRNA.
DR EMBL; X03251; CAA27012.1; -; Genomic_DNA.
DR EMBL; J03037; AAA51908.1; -; mRNA.
DR EMBL; CR536526; CAG38763.1; -; mRNA.
DR EMBL; CR541875; CAG46673.1; -; mRNA.
DR EMBL; AK312978; BAG35815.1; -; mRNA.
DR EMBL; CH471068; EAW87136.1; -; Genomic_DNA.
DR EMBL; BC011949; AAH11949.1; -; mRNA.
DR EMBL; M36532; AAA51911.1; -; mRNA.
DR PIR; A27175; CRHU2.
DR RefSeq; NP_000058.1; NM_000067.2.
DR UniGene; Hs.155097; -.
DR PDB; 12CA; X-ray; 2.40 A; A=2-260.
DR PDB; 1A42; X-ray; 2.25 A; A=2-260.
DR PDB; 1AM6; X-ray; 2.00 A; A=2-260.
DR PDB; 1AVN; X-ray; 2.00 A; A=2-260.
DR PDB; 1BCD; X-ray; 1.90 A; A=2-260.
DR PDB; 1BIC; X-ray; 1.90 A; A=2-260.
DR PDB; 1BN1; X-ray; 2.10 A; A=2-260.
DR PDB; 1BN3; X-ray; 2.20 A; A=2-260.
DR PDB; 1BN4; X-ray; 2.10 A; A=2-260.
DR PDB; 1BNM; X-ray; 2.60 A; A=2-260.
DR PDB; 1BNN; X-ray; 2.30 A; A=2-260.
DR PDB; 1BNQ; X-ray; 2.40 A; A=2-260.
DR PDB; 1BNT; X-ray; 2.15 A; A=2-260.
DR PDB; 1BNU; X-ray; 2.15 A; A=2-260.
DR PDB; 1BNV; X-ray; 2.40 A; A=2-260.
DR PDB; 1BNW; X-ray; 2.25 A; A=2-260.
DR PDB; 1BV3; X-ray; 1.85 A; A=2-260.
DR PDB; 1CA2; X-ray; 2.00 A; A=2-260.
DR PDB; 1CA3; X-ray; 2.30 A; A=2-260.
DR PDB; 1CAH; X-ray; 1.88 A; A=2-260.
DR PDB; 1CAI; X-ray; 1.80 A; A=2-260.
DR PDB; 1CAJ; X-ray; 1.90 A; A=2-260.
DR PDB; 1CAK; X-ray; 1.90 A; A=2-260.
DR PDB; 1CAL; X-ray; 2.20 A; A=2-260.
DR PDB; 1CAM; X-ray; 1.70 A; A=2-260.
DR PDB; 1CAN; X-ray; 1.90 A; A=2-260.
DR PDB; 1CAO; X-ray; 1.90 A; A=2-260.
DR PDB; 1CAY; X-ray; 2.10 A; A=2-260.
DR PDB; 1CAZ; X-ray; 1.90 A; A=2-260.
DR PDB; 1CCS; X-ray; 2.35 A; A=2-260.
DR PDB; 1CCT; X-ray; 2.20 A; A=2-260.
DR PDB; 1CCU; X-ray; 2.25 A; A=2-260.
DR PDB; 1CIL; X-ray; 1.60 A; A=2-260.
DR PDB; 1CIM; X-ray; 2.10 A; A=2-260.
DR PDB; 1CIN; X-ray; 2.10 A; A=2-260.
DR PDB; 1CNB; X-ray; 2.35 A; A=2-260.
DR PDB; 1CNC; X-ray; 2.20 A; A=2-260.
DR PDB; 1CNG; X-ray; 1.90 A; A=2-260.
DR PDB; 1CNH; X-ray; 2.05 A; A=2-260.
DR PDB; 1CNI; X-ray; 1.80 A; A=2-260.
DR PDB; 1CNJ; X-ray; 1.80 A; A=2-260.
DR PDB; 1CNK; X-ray; 2.15 A; A=2-260.
DR PDB; 1CNW; X-ray; 2.00 A; A=2-260.
DR PDB; 1CNX; X-ray; 1.90 A; A=2-260.
DR PDB; 1CNY; X-ray; 2.30 A; A=2-260.
DR PDB; 1CRA; X-ray; 1.90 A; A=2-260.
DR PDB; 1CVA; X-ray; 2.25 A; A=2-260.
DR PDB; 1CVB; X-ray; 2.40 A; A=2-260.
DR PDB; 1CVC; X-ray; 2.30 A; A=2-260.
DR PDB; 1CVD; X-ray; 2.20 A; A=2-258.
DR PDB; 1CVE; X-ray; 2.25 A; A=2-260.
DR PDB; 1CVF; X-ray; 2.25 A; A=2-260.
DR PDB; 1CVH; X-ray; 2.30 A; A=2-259.
DR PDB; 1DCA; X-ray; 2.20 A; A=2-260.
DR PDB; 1DCB; X-ray; 2.10 A; A=2-260.
DR PDB; 1EOU; X-ray; 2.10 A; A=2-260.
DR PDB; 1F2W; X-ray; 1.90 A; A=2-260.
DR PDB; 1FQL; X-ray; 2.00 A; A=2-260.
DR PDB; 1FQM; X-ray; 2.00 A; A=2-260.
DR PDB; 1FQN; X-ray; 2.00 A; A=2-260.
DR PDB; 1FQR; X-ray; 2.00 A; A=2-260.
DR PDB; 1FR4; X-ray; 1.60 A; A=2-260.
DR PDB; 1FR7; X-ray; 1.50 A; A/B=2-260.
DR PDB; 1FSN; X-ray; 2.00 A; A/B=2-260.
DR PDB; 1FSQ; X-ray; 2.00 A; A/B=2-260.
DR PDB; 1FSR; X-ray; 2.00 A; A/B=2-260.
DR PDB; 1G0E; X-ray; 1.60 A; A=2-260.
DR PDB; 1G0F; X-ray; 1.60 A; A=2-260.
DR PDB; 1G1D; X-ray; 2.04 A; A=2-260.
DR PDB; 1G3Z; X-ray; 1.86 A; A=2-260.
DR PDB; 1G45; X-ray; 1.83 A; A=2-260.
DR PDB; 1G46; X-ray; 1.84 A; A=2-260.
DR PDB; 1G48; X-ray; 1.86 A; A=2-260.
DR PDB; 1G4J; X-ray; 1.84 A; A=2-260.
DR PDB; 1G4O; X-ray; 1.96 A; A=2-260.
DR PDB; 1G52; X-ray; 1.80 A; A=2-260.
DR PDB; 1G53; X-ray; 1.94 A; A=2-260.
DR PDB; 1G54; X-ray; 1.86 A; A=2-259.
DR PDB; 1H4N; X-ray; 2.00 A; A=2-260.
DR PDB; 1H9N; X-ray; 1.85 A; A=2-260.
DR PDB; 1H9Q; X-ray; 2.20 A; A=2-260.
DR PDB; 1HCA; X-ray; 2.30 A; A=2-260.
DR PDB; 1HEA; X-ray; 2.00 A; A=2-260.
DR PDB; 1HEB; X-ray; 2.00 A; A=2-260.
DR PDB; 1HEC; X-ray; 2.00 A; A=2-260.
DR PDB; 1HED; X-ray; 2.00 A; A=2-260.
DR PDB; 1HVA; X-ray; 2.30 A; A=2-260.
DR PDB; 1I8Z; X-ray; 1.93 A; A=2-260.
DR PDB; 1I90; X-ray; 2.00 A; A=2-260.
DR PDB; 1I91; X-ray; 2.00 A; A=2-260.
DR PDB; 1I9L; X-ray; 1.93 A; A=2-260.
DR PDB; 1I9M; X-ray; 1.84 A; A=2-260.
DR PDB; 1I9N; X-ray; 1.86 A; A=2-260.
DR PDB; 1I9O; X-ray; 1.86 A; A=2-260.
DR PDB; 1I9P; X-ray; 1.92 A; A=2-260.
DR PDB; 1I9Q; X-ray; 1.80 A; A=2-260.
DR PDB; 1IF4; X-ray; 1.93 A; A=2-260.
DR PDB; 1IF5; X-ray; 2.00 A; A=2-260.
DR PDB; 1IF6; X-ray; 2.09 A; A=2-260.
DR PDB; 1IF7; X-ray; 1.98 A; A=2-260.
DR PDB; 1IF8; X-ray; 1.94 A; A=2-260.
DR PDB; 1IF9; X-ray; 2.00 A; A=2-260.
DR PDB; 1KWQ; X-ray; 2.60 A; A=2-260.
DR PDB; 1KWR; X-ray; 2.25 A; A=2-260.
DR PDB; 1LG5; X-ray; 1.75 A; A=2-260.
DR PDB; 1LG6; X-ray; 2.20 A; A=2-260.
DR PDB; 1LGD; X-ray; 1.90 A; A=2-260.
DR PDB; 1LUG; X-ray; 0.95 A; A=2-260.
DR PDB; 1LZV; X-ray; 2.30 A; A=2-260.
DR PDB; 1MOO; X-ray; 1.05 A; A=2-260.
DR PDB; 1MUA; X-ray; 1.70 A; A=2-260.
DR PDB; 1OKL; X-ray; 2.10 A; A=2-260.
DR PDB; 1OKM; X-ray; 2.20 A; A=2-260.
DR PDB; 1OKN; X-ray; 2.40 A; A=2-260.
DR PDB; 1OQ5; X-ray; 1.50 A; A=2-260.
DR PDB; 1RAY; X-ray; 1.80 A; A=2-260.
DR PDB; 1RAZ; X-ray; 1.90 A; A=2-260.
DR PDB; 1RZA; X-ray; 1.90 A; A=2-260.
DR PDB; 1RZB; X-ray; 1.80 A; A=2-260.
DR PDB; 1RZC; X-ray; 1.90 A; A=2-260.
DR PDB; 1RZD; X-ray; 1.90 A; A=2-260.
DR PDB; 1RZE; X-ray; 1.90 A; A=2-260.
DR PDB; 1T9N; X-ray; 2.00 A; A=2-260.
DR PDB; 1TB0; X-ray; 2.00 A; X=2-260.
DR PDB; 1TBT; X-ray; 2.00 A; X=2-260.
DR PDB; 1TE3; X-ray; 2.00 A; X=2-260.
DR PDB; 1TEQ; X-ray; 2.00 A; X=2-260.
DR PDB; 1TEU; X-ray; 2.00 A; X=2-260.
DR PDB; 1TG3; X-ray; 1.80 A; A=2-260.
DR PDB; 1TG9; X-ray; 1.90 A; A=2-260.
DR PDB; 1TH9; X-ray; 1.63 A; A=2-260.
DR PDB; 1THK; X-ray; 1.80 A; A=2-260.
DR PDB; 1TTM; X-ray; 1.95 A; A=2-260.
DR PDB; 1UGA; X-ray; 2.00 A; A=2-260.
DR PDB; 1UGB; X-ray; 2.00 A; A=2-260.
DR PDB; 1UGC; X-ray; 2.00 A; A=2-260.
DR PDB; 1UGD; X-ray; 2.00 A; A=2-260.
DR PDB; 1UGE; X-ray; 1.90 A; A=2-260.
DR PDB; 1UGF; X-ray; 2.00 A; A=2-260.
DR PDB; 1UGG; X-ray; 2.20 A; A=2-260.
DR PDB; 1XEG; X-ray; 1.81 A; A=2-260.
DR PDB; 1XEV; X-ray; 2.20 A; A/B/C/D=2-260.
DR PDB; 1XPZ; X-ray; 2.02 A; A=2-260.
DR PDB; 1XQ0; X-ray; 1.76 A; A=2-260.
DR PDB; 1YDA; X-ray; 2.10 A; A=2-260.
DR PDB; 1YDB; X-ray; 1.90 A; A=2-260.
DR PDB; 1YDC; X-ray; 1.95 A; A=2-260.
DR PDB; 1YDD; X-ray; 2.10 A; A=2-260.
DR PDB; 1YO0; X-ray; 1.80 A; A=2-260.
DR PDB; 1YO1; X-ray; 1.70 A; A=2-260.
DR PDB; 1YO2; X-ray; 1.80 A; A=2-260.
DR PDB; 1Z9Y; X-ray; 1.66 A; A=2-260.
DR PDB; 1ZE8; X-ray; 2.00 A; A=2-260.
DR PDB; 1ZFK; X-ray; 1.56 A; A=2-260.
DR PDB; 1ZFQ; X-ray; 1.55 A; A=2-260.
DR PDB; 1ZGE; X-ray; 1.65 A; A=2-260.
DR PDB; 1ZGF; X-ray; 1.75 A; A=2-260.
DR PDB; 1ZH9; X-ray; 1.70 A; A=2-260.
DR PDB; 1ZSA; X-ray; 2.50 A; A=2-260.
DR PDB; 1ZSB; X-ray; 2.00 A; A=2-260.
DR PDB; 1ZSC; X-ray; 1.80 A; A=2-260.
DR PDB; 2ABE; X-ray; 2.00 A; A=2-260.
DR PDB; 2AW1; X-ray; 1.46 A; A=2-260.
DR PDB; 2AX2; X-ray; 1.50 A; A=2-260.
DR PDB; 2CA2; X-ray; 1.90 A; A=2-260.
DR PDB; 2CBA; X-ray; 1.54 A; A=2-260.
DR PDB; 2CBB; X-ray; 1.67 A; A=2-260.
DR PDB; 2CBC; X-ray; 1.88 A; A=2-260.
DR PDB; 2CBD; X-ray; 1.67 A; A=2-260.
DR PDB; 2CBE; X-ray; 1.82 A; A=2-260.
DR PDB; 2EU2; X-ray; 1.15 A; A=2-260.
DR PDB; 2EU3; X-ray; 1.60 A; A=2-260.
DR PDB; 2EZ7; X-ray; 2.00 A; A=2-260.
DR PDB; 2F14; X-ray; 1.71 A; A=2-260.
DR PDB; 2FMG; X-ray; 1.60 A; A=2-260.
DR PDB; 2FMZ; X-ray; 1.60 A; A=2-260.
DR PDB; 2FNK; X-ray; 1.80 A; A=2-260.
DR PDB; 2FNM; X-ray; 1.80 A; A=2-260.
DR PDB; 2FNN; X-ray; 1.80 A; A=2-260.
DR PDB; 2FOQ; X-ray; 1.25 A; A=2-260.
DR PDB; 2FOS; X-ray; 1.10 A; A=2-260.
DR PDB; 2FOU; X-ray; 0.99 A; A=2-260.
DR PDB; 2FOV; X-ray; 1.15 A; A=2-260.
DR PDB; 2GD8; X-ray; 1.46 A; A=2-260.
DR PDB; 2GEH; X-ray; 2.00 A; A=2-260.
DR PDB; 2H15; X-ray; 1.90 A; A=2-260.
DR PDB; 2H4N; X-ray; 1.90 A; A=2-260.
DR PDB; 2HD6; X-ray; 1.80 A; A=2-260.
DR PDB; 2HKK; X-ray; 1.90 A; A=2-260.
DR PDB; 2HL4; X-ray; 1.55 A; A=2-260.
DR PDB; 2HNC; X-ray; 1.55 A; A=2-260.
DR PDB; 2HOC; X-ray; 2.10 A; A=2-260.
DR PDB; 2ILI; X-ray; 1.05 A; A=2-260.
DR PDB; 2NNG; X-ray; 1.20 A; A=2-260.
DR PDB; 2NNO; X-ray; 1.01 A; A=2-260.
DR PDB; 2NNS; X-ray; 1.03 A; A=2-260.
DR PDB; 2NNV; X-ray; 1.10 A; A=2-260.
DR PDB; 2NWO; X-ray; 1.70 A; A=2-260.
DR PDB; 2NWP; X-ray; 1.80 A; A=2-260.
DR PDB; 2NWY; X-ray; 1.65 A; A=2-260.
DR PDB; 2NWZ; X-ray; 1.80 A; A=2-260.
DR PDB; 2NXR; X-ray; 1.70 A; A=2-260.
DR PDB; 2NXS; X-ray; 1.80 A; A=2-260.
DR PDB; 2NXT; X-ray; 1.15 A; A=2-260.
DR PDB; 2O4Z; X-ray; 2.10 A; A=2-260.
DR PDB; 2OSF; X-ray; 1.60 A; A=2-260.
DR PDB; 2OSM; X-ray; 1.60 A; A=2-260.
DR PDB; 2POU; X-ray; 1.60 A; A=2-260.
DR PDB; 2POV; X-ray; 1.60 A; A=2-260.
DR PDB; 2POW; X-ray; 1.75 A; A=2-260.
DR PDB; 2Q1B; X-ray; 1.70 A; A=2-260.
DR PDB; 2Q1Q; X-ray; 1.90 A; A=2-260.
DR PDB; 2Q38; X-ray; 1.95 A; A=2-260.
DR PDB; 2QO8; X-ray; 1.40 A; A=2-260.
DR PDB; 2QOA; X-ray; 1.60 A; A=2-260.
DR PDB; 2QP6; X-ray; 1.45 A; A=2-260.
DR PDB; 2VVA; X-ray; 1.56 A; X=2-260.
DR PDB; 2VVB; X-ray; 1.66 A; X=2-260.
DR PDB; 2WD2; X-ray; 1.49 A; A=2-260.
DR PDB; 2WD3; X-ray; 1.80 A; A=2-260.
DR PDB; 2WEG; X-ray; 1.10 A; A=2-260.
DR PDB; 2WEH; X-ray; 2.09 A; A=2-260.
DR PDB; 2WEJ; X-ray; 1.45 A; A=2-260.
DR PDB; 2WEO; X-ray; 1.40 A; A=2-260.
DR PDB; 2X7S; X-ray; 1.64 A; A=2-260.
DR PDB; 2X7T; X-ray; 1.89 A; A=2-260.
DR PDB; 2X7U; X-ray; 2.12 A; A=2-260.
DR PDB; 3B4F; X-ray; 1.89 A; A=2-260.
DR PDB; 3BET; X-ray; 1.85 A; A=2-260.
DR PDB; 3BL0; X-ray; 1.90 A; A=2-260.
DR PDB; 3BL1; X-ray; 2.10 A; A=2-260.
DR PDB; 3C7P; X-ray; 1.70 A; A=2-260.
DR PDB; 3CA2; X-ray; 2.00 A; A=2-260.
DR PDB; 3CAJ; X-ray; 1.80 A; A=2-260.
DR PDB; 3CYU; X-ray; 1.70 A; A=2-260.
DR PDB; 3D8W; X-ray; 1.70 A; A=2-260.
DR PDB; 3D92; X-ray; 1.10 A; A=2-260.
DR PDB; 3D93; X-ray; 1.10 A; A=2-260.
DR PDB; 3D9Z; X-ray; 1.65 A; A=2-260.
DR PDB; 3DAZ; X-ray; 1.60 A; A=2-260.
DR PDB; 3DBU; X-ray; 1.70 A; A=2-260.
DR PDB; 3DC3; X-ray; 1.70 A; A=2-260.
DR PDB; 3DC9; X-ray; 1.60 A; A=2-260.
DR PDB; 3DCC; X-ray; 1.60 A; A=2-260.
DR PDB; 3DCS; X-ray; 1.80 A; A=2-260.
DR PDB; 3DCW; X-ray; 1.50 A; A=2-260.
DR PDB; 3DD0; X-ray; 1.48 A; A=2-260.
DR PDB; 3DD8; X-ray; 1.90 A; A=2-260.
DR PDB; 3DV7; X-ray; 1.70 A; A=2-260.
DR PDB; 3DVB; X-ray; 1.70 A; A=2-260.
DR PDB; 3DVC; X-ray; 1.60 A; A=2-260.
DR PDB; 3DVD; X-ray; 1.60 A; A=2-260.
DR PDB; 3EFI; X-ray; 1.75 A; A=2-260.
DR PDB; 3EFT; X-ray; 1.85 A; A=1-260.
DR PDB; 3F4X; X-ray; 1.90 A; A=2-260.
DR PDB; 3F8E; X-ray; 2.00 A; A=1-260.
DR PDB; 3FFP; X-ray; 1.81 A; X=1-260.
DR PDB; 3GZ0; X-ray; 1.26 A; A=2-260.
DR PDB; 3HFP; X-ray; 2.10 A; A=1-260.
DR PDB; 3HKN; X-ray; 1.80 A; A=1-260.
DR PDB; 3HKQ; X-ray; 1.70 A; A=1-260.
DR PDB; 3HKT; X-ray; 2.36 A; A=1-260.
DR PDB; 3HKU; X-ray; 1.80 A; A=1-260.
DR PDB; 3HLJ; X-ray; 1.44 A; A=1-260.
DR PDB; 3HS4; X-ray; 1.10 A; A=1-260.
DR PDB; 3IBI; X-ray; 1.93 A; A=2-260.
DR PDB; 3IBL; X-ray; 1.55 A; A=2-260.
DR PDB; 3IBN; X-ray; 2.20 A; A=2-260.
DR PDB; 3IBU; X-ray; 1.41 A; A=2-260.
DR PDB; 3IEO; X-ray; 2.00 A; A=1-260.
DR PDB; 3IGP; X-ray; 1.65 A; A=1-260.
DR PDB; 3K2F; X-ray; 1.98 A; A=1-260.
DR PDB; 3K34; X-ray; 0.90 A; A=1-260.
DR PDB; 3K7K; X-ray; 1.90 A; A=1-260.
DR PDB; 3KIG; X-ray; 1.39 A; A=1-260.
DR PDB; 3KKX; Neutron; 2.00 A; A=1-260.
DR PDB; 3KNE; X-ray; 1.35 A; A=1-260.
DR PDB; 3KOI; X-ray; 1.64 A; A=1-260.
DR PDB; 3KOK; X-ray; 1.50 A; A=1-260.
DR PDB; 3KON; X-ray; 1.50 A; A=1-260.
DR PDB; 3KS3; X-ray; 0.90 A; A=1-260.
DR PDB; 3KWA; X-ray; 2.00 A; A=1-260.
DR PDB; 3L14; X-ray; 1.22 A; A=1-260.
DR PDB; 3M04; X-ray; 1.40 A; A=1-260.
DR PDB; 3M14; X-ray; 1.38 A; A=1-260.
DR PDB; 3M1J; X-ray; 1.80 A; A=1-260.
DR PDB; 3M1K; X-ray; 1.35 A; A=1-260.
DR PDB; 3M1Q; X-ray; 1.69 A; A=1-260.
DR PDB; 3M1W; X-ray; 1.38 A; A=1-260.
DR PDB; 3M2N; X-ray; 1.65 A; A=1-260.
DR PDB; 3M2X; X-ray; 1.87 A; A=1-260.
DR PDB; 3M2Y; X-ray; 1.17 A; A=1-260.
DR PDB; 3M2Z; X-ray; 1.70 A; A=1-260.
DR PDB; 3M3X; X-ray; 1.68 A; A=1-260.
DR PDB; 3M40; X-ray; 1.60 A; A=1-260.
DR PDB; 3M5E; X-ray; 1.70 A; A=1-260.
DR PDB; 3M5S; X-ray; 1.40 A; A=1-260.
DR PDB; 3M5T; X-ray; 1.95 A; A=1-260.
DR PDB; 3M67; X-ray; 1.80 A; A=1-260.
DR PDB; 3M96; X-ray; 1.40 A; A=1-260.
DR PDB; 3M98; X-ray; 1.50 A; A=1-260.
DR PDB; 3MHC; X-ray; 1.70 A; A=1-260.
DR PDB; 3MHI; X-ray; 1.70 A; A=1-260.
DR PDB; 3MHL; X-ray; 1.90 A; A=1-260.
DR PDB; 3MHM; X-ray; 1.50 A; A=1-260.
DR PDB; 3MHO; X-ray; 1.15 A; A=1-260.
DR PDB; 3ML2; X-ray; 1.80 A; A=1-260.
DR PDB; 3MMF; X-ray; 1.50 A; A=1-260.
DR PDB; 3MNA; X-ray; 1.50 A; A=1-260.
DR PDB; 3MNH; X-ray; 1.65 A; A=1-260.
DR PDB; 3MNI; X-ray; 1.75 A; A=1-260.
DR PDB; 3MNJ; X-ray; 1.75 A; A=1-260.
DR PDB; 3MNK; X-ray; 1.75 A; A=1-260.
DR PDB; 3MNU; X-ray; 1.80 A; A=2-260.
DR PDB; 3MWO; X-ray; 1.40 A; A/B=1-260.
DR PDB; 3MYQ; X-ray; 1.35 A; A=1-260.
DR PDB; 3MZC; X-ray; 1.50 A; A=1-260.
DR PDB; 3N0N; X-ray; 1.50 A; A=1-260.
DR PDB; 3N2P; X-ray; 1.65 A; A=1-260.
DR PDB; 3N3J; X-ray; 1.50 A; A=1-260.
DR PDB; 3N4B; X-ray; 1.60 A; A=1-260.
DR PDB; 3NB5; X-ray; 1.80 A; A=1-260.
DR PDB; 3NI5; X-ray; 2.10 A; A=1-260.
DR PDB; 3NJ9; X-ray; 2.00 A; A=1-260.
DR PDB; 3OIK; X-ray; 1.50 A; A=1-260.
DR PDB; 3OIL; X-ray; 1.50 A; A=1-260.
DR PDB; 3OIM; X-ray; 1.45 A; A=1-260.
DR PDB; 3OKU; X-ray; 1.45 A; A=1-260.
DR PDB; 3OKV; X-ray; 1.45 A; A=1-260.
DR PDB; 3OY0; X-ray; 1.60 A; A=1-260.
DR PDB; 3OYQ; X-ray; 1.47 A; A=1-260.
DR PDB; 3OYS; X-ray; 1.54 A; A=1-260.
DR PDB; 3P3H; X-ray; 1.50 A; A=1-260.
DR PDB; 3P3J; X-ray; 1.60 A; A=1-260.
DR PDB; 3P44; X-ray; 2.20 A; A=1-260.
DR PDB; 3P4V; X-ray; 2.00 A; A=1-260.
DR PDB; 3P55; X-ray; 2.00 A; A=1-260.
DR PDB; 3P58; X-ray; 1.49 A; A=1-260.
DR PDB; 3P5A; X-ray; 1.49 A; A=1-260.
DR PDB; 3P5L; X-ray; 1.50 A; A=1-260.
DR PDB; 3PJJ; X-ray; 1.80 A; A=2-260.
DR PDB; 3PO6; X-ray; 1.47 A; A=2-260.
DR PDB; 3PYK; X-ray; 1.30 A; A=3-260.
DR PDB; 3QYK; X-ray; 1.47 A; A=1-260.
DR PDB; 3R16; X-ray; 1.60 A; A=4-260.
DR PDB; 3R17; X-ray; 1.70 A; B=4-260.
DR PDB; 3RG3; X-ray; 1.90 A; A=1-260.
DR PDB; 3RG4; X-ray; 1.50 A; A=1-260.
DR PDB; 3RGE; X-ray; 2.10 A; A=1-260.
DR PDB; 3RJ7; X-ray; 1.20 A; A=3-260.
DR PDB; 3RLD; X-ray; 1.50 A; A=1-260.
DR PDB; 3RYJ; X-ray; 1.39 A; B=2-260.
DR PDB; 3RYV; X-ray; 1.20 A; B=2-260.
DR PDB; 3RYX; X-ray; 1.60 A; B=2-260.
DR PDB; 3RYY; X-ray; 1.16 A; A=2-260.
DR PDB; 3RYZ; X-ray; 1.37 A; A=2-260.
DR PDB; 3RZ0; X-ray; 1.80 A; B=2-260.
DR PDB; 3RZ1; X-ray; 1.51 A; B=2-260.
DR PDB; 3RZ5; X-ray; 1.65 A; A=2-260.
DR PDB; 3RZ7; X-ray; 1.80 A; A=2-260.
DR PDB; 3RZ8; X-ray; 1.70 A; A=2-260.
DR PDB; 3S71; X-ray; 1.25 A; B=3-260.
DR PDB; 3S72; X-ray; 1.60 A; B=3-260.
DR PDB; 3S73; X-ray; 1.75 A; B=3-260.
DR PDB; 3S74; X-ray; 1.40 A; B=3-260.
DR PDB; 3S75; X-ray; 1.50 A; B=3-260.
DR PDB; 3S76; X-ray; 1.60 A; A=3-260.
DR PDB; 3S77; X-ray; 1.86 A; B=3-260.
DR PDB; 3S78; X-ray; 1.98 A; B=3-260.
DR PDB; 3S8X; X-ray; 1.30 A; A=1-260.
DR PDB; 3S9T; X-ray; 1.30 A; A=1-260.
DR PDB; 3SAP; X-ray; 1.75 A; A=1-260.
DR PDB; 3SAX; X-ray; 1.10 A; A=1-260.
DR PDB; 3SBH; X-ray; 1.65 A; A=1-260.
DR PDB; 3SBI; X-ray; 1.40 A; A=1-260.
DR PDB; 3T5U; X-ray; 1.75 A; A=2-260.
DR PDB; 3T5Z; X-ray; 1.65 A; A=2-260.
DR PDB; 3T82; X-ray; 2.00 A; A=1-260.
DR PDB; 3T83; X-ray; 1.80 A; A=1-260.
DR PDB; 3T84; X-ray; 2.00 A; A=1-260.
DR PDB; 3T85; X-ray; 2.40 A; A=1-260.
DR PDB; 3TMJ; Other; 2.00 A; A=3-260.
DR PDB; 3TVN; X-ray; 1.50 A; X=3-260.
DR PDB; 3TVO; X-ray; 1.60 A; X=3-260.
DR PDB; 3U3A; X-ray; 1.55 A; X=1-260.
DR PDB; 3U45; X-ray; 1.70 A; X=1-260.
DR PDB; 3U47; X-ray; 1.60 A; A=1-260.
DR PDB; 3U7C; X-ray; 0.93 A; A=1-260.
DR PDB; 3V2J; X-ray; 1.70 A; A=1-260.
DR PDB; 3V2M; X-ray; 1.47 A; A=1-260.
DR PDB; 3V3F; X-ray; 2.00 A; A=1-260.
DR PDB; 3V3G; X-ray; 1.56 A; B=1-260.
DR PDB; 3V3H; X-ray; 1.85 A; B=1-260.
DR PDB; 3V3I; X-ray; 1.73 A; B=1-260.
DR PDB; 3V3J; X-ray; 1.63 A; A=1-260.
DR PDB; 3V5G; X-ray; 1.50 A; A=1-260.
DR PDB; 3V7X; X-ray; 1.03 A; A=2-260.
DR PDB; 3VBD; X-ray; 1.05 A; A=2-260.
DR PDB; 3ZP9; X-ray; 1.31 A; A=1-260.
DR PDB; 4BCW; X-ray; 1.50 A; A=4-260.
DR PDB; 4CA2; X-ray; 2.10 A; A=2-260.
DR PDB; 4CAC; X-ray; 2.20 A; A=2-260.
DR PDB; 4DZ7; X-ray; 1.49 A; A=1-260.
DR PDB; 4DZ9; X-ray; 1.49 A; A=1-260.
DR PDB; 4E3D; X-ray; 1.60 A; A=1-260.
DR PDB; 4E3F; X-ray; 1.50 A; A=1-260.
DR PDB; 4E3G; X-ray; 1.55 A; A=1-260.
DR PDB; 4E3H; X-ray; 1.50 A; A=1-260.
DR PDB; 4E49; X-ray; 1.45 A; A=1-260.
DR PDB; 4E4A; X-ray; 1.45 A; A=1-260.
DR PDB; 4E5Q; X-ray; 1.70 A; A=1-260.
DR PDB; 4FIK; X-ray; 1.20 A; A=1-260.
DR PDB; 4FL7; X-ray; 1.85 A; A=2-260.
DR PDB; 4FPT; X-ray; 0.98 A; A=1-260.
DR PDB; 4FRC; X-ray; 0.98 A; A=1-260.
DR PDB; 4FU5; X-ray; 0.98 A; A=1-260.
DR PDB; 4FVN; X-ray; 1.05 A; A=1-260.
DR PDB; 4FVO; X-ray; 1.05 A; A=1-260.
DR PDB; 4G0C; Neutron; 2.00 A; A=4-260.
DR PDB; 4GGE; X-ray; 1.47 A; A=1-260.
DR PDB; 4GL1; X-ray; 1.50 A; X=1-260.
DR PDB; 4HBA; X-ray; 1.76 A; A=1-260.
DR PDB; 4HEW; X-ray; 1.70 A; A=1-260.
DR PDB; 4HEY; X-ray; 1.45 A; A=1-260.
DR PDB; 4HEZ; X-ray; 1.34 A; A=1-260.
DR PDB; 4HF3; X-ray; 1.15 A; A=1-260.
DR PDB; 4HT0; X-ray; 1.60 A; A=1-260.
DR PDB; 4IDR; X-ray; 1.60 A; X=3-260.
DR PDB; 4ILX; X-ray; 1.60 A; A=4-260.
DR PDB; 4JS6; X-ray; 1.55 A; A=1-260.
DR PDB; 4JSA; X-ray; 1.50 A; A=1-260.
DR PDB; 4JSS; X-ray; 1.50 A; A=1-260.
DR PDB; 4JSW; X-ray; 1.90 A; A=1-260.
DR PDB; 4JSZ; X-ray; 1.90 A; A=1-260.
DR PDB; 4KAP; X-ray; 1.45 A; A=5-260.
DR PDB; 4KNI; X-ray; 1.80 A; A=1-260.
DR PDB; 4KNJ; X-ray; 2.00 A; A=1-260.
DR PDB; 4LP6; X-ray; 2.15 A; A/B=1-260.
DR PDB; 4M2R; X-ray; 1.99 A; A=4-260.
DR PDB; 4M2U; X-ray; 2.00 A; A=4-260.
DR PDB; 4M2V; X-ray; 1.72 A; A=4-260.
DR PDB; 4M2W; X-ray; 1.66 A; A=4-260.
DR PDB; 4MO8; X-ray; 1.85 A; A=1-260.
DR PDB; 5CA2; X-ray; 2.10 A; A=2-260.
DR PDB; 5CAC; X-ray; 2.20 A; A=2-260.
DR PDB; 6CA2; X-ray; 2.50 A; A=2-260.
DR PDB; 7CA2; X-ray; 2.40 A; A=2-260.
DR PDB; 8CA2; X-ray; 2.40 A; A=2-260.
DR PDB; 9CA2; X-ray; 2.80 A; A=2-260.
DR PDBsum; 12CA; -.
DR PDBsum; 1A42; -.
DR PDBsum; 1AM6; -.
DR PDBsum; 1AVN; -.
DR PDBsum; 1BCD; -.
DR PDBsum; 1BIC; -.
DR PDBsum; 1BN1; -.
DR PDBsum; 1BN3; -.
DR PDBsum; 1BN4; -.
DR PDBsum; 1BNM; -.
DR PDBsum; 1BNN; -.
DR PDBsum; 1BNQ; -.
DR PDBsum; 1BNT; -.
DR PDBsum; 1BNU; -.
DR PDBsum; 1BNV; -.
DR PDBsum; 1BNW; -.
DR PDBsum; 1BV3; -.
DR PDBsum; 1CA2; -.
DR PDBsum; 1CA3; -.
DR PDBsum; 1CAH; -.
DR PDBsum; 1CAI; -.
DR PDBsum; 1CAJ; -.
DR PDBsum; 1CAK; -.
DR PDBsum; 1CAL; -.
DR PDBsum; 1CAM; -.
DR PDBsum; 1CAN; -.
DR PDBsum; 1CAO; -.
DR PDBsum; 1CAY; -.
DR PDBsum; 1CAZ; -.
DR PDBsum; 1CCS; -.
DR PDBsum; 1CCT; -.
DR PDBsum; 1CCU; -.
DR PDBsum; 1CIL; -.
DR PDBsum; 1CIM; -.
DR PDBsum; 1CIN; -.
DR PDBsum; 1CNB; -.
DR PDBsum; 1CNC; -.
DR PDBsum; 1CNG; -.
DR PDBsum; 1CNH; -.
DR PDBsum; 1CNI; -.
DR PDBsum; 1CNJ; -.
DR PDBsum; 1CNK; -.
DR PDBsum; 1CNW; -.
DR PDBsum; 1CNX; -.
DR PDBsum; 1CNY; -.
DR PDBsum; 1CRA; -.
DR PDBsum; 1CVA; -.
DR PDBsum; 1CVB; -.
DR PDBsum; 1CVC; -.
DR PDBsum; 1CVD; -.
DR PDBsum; 1CVE; -.
DR PDBsum; 1CVF; -.
DR PDBsum; 1CVH; -.
DR PDBsum; 1DCA; -.
DR PDBsum; 1DCB; -.
DR PDBsum; 1EOU; -.
DR PDBsum; 1F2W; -.
DR PDBsum; 1FQL; -.
DR PDBsum; 1FQM; -.
DR PDBsum; 1FQN; -.
DR PDBsum; 1FQR; -.
DR PDBsum; 1FR4; -.
DR PDBsum; 1FR7; -.
DR PDBsum; 1FSN; -.
DR PDBsum; 1FSQ; -.
DR PDBsum; 1FSR; -.
DR PDBsum; 1G0E; -.
DR PDBsum; 1G0F; -.
DR PDBsum; 1G1D; -.
DR PDBsum; 1G3Z; -.
DR PDBsum; 1G45; -.
DR PDBsum; 1G46; -.
DR PDBsum; 1G48; -.
DR PDBsum; 1G4J; -.
DR PDBsum; 1G4O; -.
DR PDBsum; 1G52; -.
DR PDBsum; 1G53; -.
DR PDBsum; 1G54; -.
DR PDBsum; 1H4N; -.
DR PDBsum; 1H9N; -.
DR PDBsum; 1H9Q; -.
DR PDBsum; 1HCA; -.
DR PDBsum; 1HEA; -.
DR PDBsum; 1HEB; -.
DR PDBsum; 1HEC; -.
DR PDBsum; 1HED; -.
DR PDBsum; 1HVA; -.
DR PDBsum; 1I8Z; -.
DR PDBsum; 1I90; -.
DR PDBsum; 1I91; -.
DR PDBsum; 1I9L; -.
DR PDBsum; 1I9M; -.
DR PDBsum; 1I9N; -.
DR PDBsum; 1I9O; -.
DR PDBsum; 1I9P; -.
DR PDBsum; 1I9Q; -.
DR PDBsum; 1IF4; -.
DR PDBsum; 1IF5; -.
DR PDBsum; 1IF6; -.
DR PDBsum; 1IF7; -.
DR PDBsum; 1IF8; -.
DR PDBsum; 1IF9; -.
DR PDBsum; 1KWQ; -.
DR PDBsum; 1KWR; -.
DR PDBsum; 1LG5; -.
DR PDBsum; 1LG6; -.
DR PDBsum; 1LGD; -.
DR PDBsum; 1LUG; -.
DR PDBsum; 1LZV; -.
DR PDBsum; 1MOO; -.
DR PDBsum; 1MUA; -.
DR PDBsum; 1OKL; -.
DR PDBsum; 1OKM; -.
DR PDBsum; 1OKN; -.
DR PDBsum; 1OQ5; -.
DR PDBsum; 1RAY; -.
DR PDBsum; 1RAZ; -.
DR PDBsum; 1RZA; -.
DR PDBsum; 1RZB; -.
DR PDBsum; 1RZC; -.
DR PDBsum; 1RZD; -.
DR PDBsum; 1RZE; -.
DR PDBsum; 1T9N; -.
DR PDBsum; 1TB0; -.
DR PDBsum; 1TBT; -.
DR PDBsum; 1TE3; -.
DR PDBsum; 1TEQ; -.
DR PDBsum; 1TEU; -.
DR PDBsum; 1TG3; -.
DR PDBsum; 1TG9; -.
DR PDBsum; 1TH9; -.
DR PDBsum; 1THK; -.
DR PDBsum; 1TTM; -.
DR PDBsum; 1UGA; -.
DR PDBsum; 1UGB; -.
DR PDBsum; 1UGC; -.
DR PDBsum; 1UGD; -.
DR PDBsum; 1UGE; -.
DR PDBsum; 1UGF; -.
DR PDBsum; 1UGG; -.
DR PDBsum; 1XEG; -.
DR PDBsum; 1XEV; -.
DR PDBsum; 1XPZ; -.
DR PDBsum; 1XQ0; -.
DR PDBsum; 1YDA; -.
DR PDBsum; 1YDB; -.
DR PDBsum; 1YDC; -.
DR PDBsum; 1YDD; -.
DR PDBsum; 1YO0; -.
DR PDBsum; 1YO1; -.
DR PDBsum; 1YO2; -.
DR PDBsum; 1Z9Y; -.
DR PDBsum; 1ZE8; -.
DR PDBsum; 1ZFK; -.
DR PDBsum; 1ZFQ; -.
DR PDBsum; 1ZGE; -.
DR PDBsum; 1ZGF; -.
DR PDBsum; 1ZH9; -.
DR PDBsum; 1ZSA; -.
DR PDBsum; 1ZSB; -.
DR PDBsum; 1ZSC; -.
DR PDBsum; 2ABE; -.
DR PDBsum; 2AW1; -.
DR PDBsum; 2AX2; -.
DR PDBsum; 2CA2; -.
DR PDBsum; 2CBA; -.
DR PDBsum; 2CBB; -.
DR PDBsum; 2CBC; -.
DR PDBsum; 2CBD; -.
DR PDBsum; 2CBE; -.
DR PDBsum; 2EU2; -.
DR PDBsum; 2EU3; -.
DR PDBsum; 2EZ7; -.
DR PDBsum; 2F14; -.
DR PDBsum; 2FMG; -.
DR PDBsum; 2FMZ; -.
DR PDBsum; 2FNK; -.
DR PDBsum; 2FNM; -.
DR PDBsum; 2FNN; -.
DR PDBsum; 2FOQ; -.
DR PDBsum; 2FOS; -.
DR PDBsum; 2FOU; -.
DR PDBsum; 2FOV; -.
DR PDBsum; 2GD8; -.
DR PDBsum; 2GEH; -.
DR PDBsum; 2H15; -.
DR PDBsum; 2H4N; -.
DR PDBsum; 2HD6; -.
DR PDBsum; 2HKK; -.
DR PDBsum; 2HL4; -.
DR PDBsum; 2HNC; -.
DR PDBsum; 2HOC; -.
DR PDBsum; 2ILI; -.
DR PDBsum; 2NNG; -.
DR PDBsum; 2NNO; -.
DR PDBsum; 2NNS; -.
DR PDBsum; 2NNV; -.
DR PDBsum; 2NWO; -.
DR PDBsum; 2NWP; -.
DR PDBsum; 2NWY; -.
DR PDBsum; 2NWZ; -.
DR PDBsum; 2NXR; -.
DR PDBsum; 2NXS; -.
DR PDBsum; 2NXT; -.
DR PDBsum; 2O4Z; -.
DR PDBsum; 2OSF; -.
DR PDBsum; 2OSM; -.
DR PDBsum; 2POU; -.
DR PDBsum; 2POV; -.
DR PDBsum; 2POW; -.
DR PDBsum; 2Q1B; -.
DR PDBsum; 2Q1Q; -.
DR PDBsum; 2Q38; -.
DR PDBsum; 2QO8; -.
DR PDBsum; 2QOA; -.
DR PDBsum; 2QP6; -.
DR PDBsum; 2VVA; -.
DR PDBsum; 2VVB; -.
DR PDBsum; 2WD2; -.
DR PDBsum; 2WD3; -.
DR PDBsum; 2WEG; -.
DR PDBsum; 2WEH; -.
DR PDBsum; 2WEJ; -.
DR PDBsum; 2WEO; -.
DR PDBsum; 2X7S; -.
DR PDBsum; 2X7T; -.
DR PDBsum; 2X7U; -.
DR PDBsum; 3B4F; -.
DR PDBsum; 3BET; -.
DR PDBsum; 3BL0; -.
DR PDBsum; 3BL1; -.
DR PDBsum; 3C7P; -.
DR PDBsum; 3CA2; -.
DR PDBsum; 3CAJ; -.
DR PDBsum; 3CYU; -.
DR PDBsum; 3D8W; -.
DR PDBsum; 3D92; -.
DR PDBsum; 3D93; -.
DR PDBsum; 3D9Z; -.
DR PDBsum; 3DAZ; -.
DR PDBsum; 3DBU; -.
DR PDBsum; 3DC3; -.
DR PDBsum; 3DC9; -.
DR PDBsum; 3DCC; -.
DR PDBsum; 3DCS; -.
DR PDBsum; 3DCW; -.
DR PDBsum; 3DD0; -.
DR PDBsum; 3DD8; -.
DR PDBsum; 3DV7; -.
DR PDBsum; 3DVB; -.
DR PDBsum; 3DVC; -.
DR PDBsum; 3DVD; -.
DR PDBsum; 3EFI; -.
DR PDBsum; 3EFT; -.
DR PDBsum; 3F4X; -.
DR PDBsum; 3F8E; -.
DR PDBsum; 3FFP; -.
DR PDBsum; 3GZ0; -.
DR PDBsum; 3HFP; -.
DR PDBsum; 3HKN; -.
DR PDBsum; 3HKQ; -.
DR PDBsum; 3HKT; -.
DR PDBsum; 3HKU; -.
DR PDBsum; 3HLJ; -.
DR PDBsum; 3HS4; -.
DR PDBsum; 3IBI; -.
DR PDBsum; 3IBL; -.
DR PDBsum; 3IBN; -.
DR PDBsum; 3IBU; -.
DR PDBsum; 3IEO; -.
DR PDBsum; 3IGP; -.
DR PDBsum; 3K2F; -.
DR PDBsum; 3K34; -.
DR PDBsum; 3K7K; -.
DR PDBsum; 3KIG; -.
DR PDBsum; 3KKX; -.
DR PDBsum; 3KNE; -.
DR PDBsum; 3KOI; -.
DR PDBsum; 3KOK; -.
DR PDBsum; 3KON; -.
DR PDBsum; 3KS3; -.
DR PDBsum; 3KWA; -.
DR PDBsum; 3L14; -.
DR PDBsum; 3M04; -.
DR PDBsum; 3M14; -.
DR PDBsum; 3M1J; -.
DR PDBsum; 3M1K; -.
DR PDBsum; 3M1Q; -.
DR PDBsum; 3M1W; -.
DR PDBsum; 3M2N; -.
DR PDBsum; 3M2X; -.
DR PDBsum; 3M2Y; -.
DR PDBsum; 3M2Z; -.
DR PDBsum; 3M3X; -.
DR PDBsum; 3M40; -.
DR PDBsum; 3M5E; -.
DR PDBsum; 3M5S; -.
DR PDBsum; 3M5T; -.
DR PDBsum; 3M67; -.
DR PDBsum; 3M96; -.
DR PDBsum; 3M98; -.
DR PDBsum; 3MHC; -.
DR PDBsum; 3MHI; -.
DR PDBsum; 3MHL; -.
DR PDBsum; 3MHM; -.
DR PDBsum; 3MHO; -.
DR PDBsum; 3ML2; -.
DR PDBsum; 3MMF; -.
DR PDBsum; 3MNA; -.
DR PDBsum; 3MNH; -.
DR PDBsum; 3MNI; -.
DR PDBsum; 3MNJ; -.
DR PDBsum; 3MNK; -.
DR PDBsum; 3MNU; -.
DR PDBsum; 3MWO; -.
DR PDBsum; 3MYQ; -.
DR PDBsum; 3MZC; -.
DR PDBsum; 3N0N; -.
DR PDBsum; 3N2P; -.
DR PDBsum; 3N3J; -.
DR PDBsum; 3N4B; -.
DR PDBsum; 3NB5; -.
DR PDBsum; 3NI5; -.
DR PDBsum; 3NJ9; -.
DR PDBsum; 3OIK; -.
DR PDBsum; 3OIL; -.
DR PDBsum; 3OIM; -.
DR PDBsum; 3OKU; -.
DR PDBsum; 3OKV; -.
DR PDBsum; 3OY0; -.
DR PDBsum; 3OYQ; -.
DR PDBsum; 3OYS; -.
DR PDBsum; 3P3H; -.
DR PDBsum; 3P3J; -.
DR PDBsum; 3P44; -.
DR PDBsum; 3P4V; -.
DR PDBsum; 3P55; -.
DR PDBsum; 3P58; -.
DR PDBsum; 3P5A; -.
DR PDBsum; 3P5L; -.
DR PDBsum; 3PJJ; -.
DR PDBsum; 3PO6; -.
DR PDBsum; 3PYK; -.
DR PDBsum; 3QYK; -.
DR PDBsum; 3R16; -.
DR PDBsum; 3R17; -.
DR PDBsum; 3RG3; -.
DR PDBsum; 3RG4; -.
DR PDBsum; 3RGE; -.
DR PDBsum; 3RJ7; -.
DR PDBsum; 3RLD; -.
DR PDBsum; 3RYJ; -.
DR PDBsum; 3RYV; -.
DR PDBsum; 3RYX; -.
DR PDBsum; 3RYY; -.
DR PDBsum; 3RYZ; -.
DR PDBsum; 3RZ0; -.
DR PDBsum; 3RZ1; -.
DR PDBsum; 3RZ5; -.
DR PDBsum; 3RZ7; -.
DR PDBsum; 3RZ8; -.
DR PDBsum; 3S71; -.
DR PDBsum; 3S72; -.
DR PDBsum; 3S73; -.
DR PDBsum; 3S74; -.
DR PDBsum; 3S75; -.
DR PDBsum; 3S76; -.
DR PDBsum; 3S77; -.
DR PDBsum; 3S78; -.
DR PDBsum; 3S8X; -.
DR PDBsum; 3S9T; -.
DR PDBsum; 3SAP; -.
DR PDBsum; 3SAX; -.
DR PDBsum; 3SBH; -.
DR PDBsum; 3SBI; -.
DR PDBsum; 3T5U; -.
DR PDBsum; 3T5Z; -.
DR PDBsum; 3T82; -.
DR PDBsum; 3T83; -.
DR PDBsum; 3T84; -.
DR PDBsum; 3T85; -.
DR PDBsum; 3TMJ; -.
DR PDBsum; 3TVN; -.
DR PDBsum; 3TVO; -.
DR PDBsum; 3U3A; -.
DR PDBsum; 3U45; -.
DR PDBsum; 3U47; -.
DR PDBsum; 3U7C; -.
DR PDBsum; 3V2J; -.
DR PDBsum; 3V2M; -.
DR PDBsum; 3V3F; -.
DR PDBsum; 3V3G; -.
DR PDBsum; 3V3H; -.
DR PDBsum; 3V3I; -.
DR PDBsum; 3V3J; -.
DR PDBsum; 3V5G; -.
DR PDBsum; 3V7X; -.
DR PDBsum; 3VBD; -.
DR PDBsum; 3ZP9; -.
DR PDBsum; 4BCW; -.
DR PDBsum; 4CA2; -.
DR PDBsum; 4CAC; -.
DR PDBsum; 4DZ7; -.
DR PDBsum; 4DZ9; -.
DR PDBsum; 4E3D; -.
DR PDBsum; 4E3F; -.
DR PDBsum; 4E3G; -.
DR PDBsum; 4E3H; -.
DR PDBsum; 4E49; -.
DR PDBsum; 4E4A; -.
DR PDBsum; 4E5Q; -.
DR PDBsum; 4FIK; -.
DR PDBsum; 4FL7; -.
DR PDBsum; 4FPT; -.
DR PDBsum; 4FRC; -.
DR PDBsum; 4FU5; -.
DR PDBsum; 4FVN; -.
DR PDBsum; 4FVO; -.
DR PDBsum; 4G0C; -.
DR PDBsum; 4GGE; -.
DR PDBsum; 4GL1; -.
DR PDBsum; 4HBA; -.
DR PDBsum; 4HEW; -.
DR PDBsum; 4HEY; -.
DR PDBsum; 4HEZ; -.
DR PDBsum; 4HF3; -.
DR PDBsum; 4HT0; -.
DR PDBsum; 4IDR; -.
DR PDBsum; 4ILX; -.
DR PDBsum; 4JS6; -.
DR PDBsum; 4JSA; -.
DR PDBsum; 4JSS; -.
DR PDBsum; 4JSW; -.
DR PDBsum; 4JSZ; -.
DR PDBsum; 4KAP; -.
DR PDBsum; 4KNI; -.
DR PDBsum; 4KNJ; -.
DR PDBsum; 4LP6; -.
DR PDBsum; 4M2R; -.
DR PDBsum; 4M2U; -.
DR PDBsum; 4M2V; -.
DR PDBsum; 4M2W; -.
DR PDBsum; 4MO8; -.
DR PDBsum; 5CA2; -.
DR PDBsum; 5CAC; -.
DR PDBsum; 6CA2; -.
DR PDBsum; 7CA2; -.
DR PDBsum; 8CA2; -.
DR PDBsum; 9CA2; -.
DR ProteinModelPortal; P00918; -.
DR SMR; P00918; 3-260.
DR IntAct; P00918; 5.
DR MINT; MINT-1367766; -.
DR STRING; 9606.ENSP00000285379; -.
DR BindingDB; P00918; -.
DR ChEMBL; CHEMBL205; -.
DR DrugBank; DB00819; Acetazolamide.
DR DrugBank; DB00436; Bendroflumethiazide.
DR DrugBank; DB00562; Benzthiazide.
DR DrugBank; DB01194; Brinzolamide.
DR DrugBank; DB00880; Chlorothiazide.
DR DrugBank; DB00606; Cyclothiazide.
DR DrugBank; DB01119; Diazoxide.
DR DrugBank; DB00869; Dorzolamide.
DR DrugBank; DB01031; Ethinamate.
DR DrugBank; DB00999; Hydrochlorothiazide.
DR DrugBank; DB00774; Hydroflumethiazide.
DR DrugBank; DB00232; Methyclothiazide.
DR DrugBank; DB01325; Quinethazone.
DR DrugBank; DB00273; Topiramate.
DR DrugBank; DB01021; Trichlormethiazide.
DR PhosphoSite; P00918; -.
DR DMDM; 115456; -.
DR OGP; P00918; -.
DR REPRODUCTION-2DPAGE; IPI00218414; -.
DR REPRODUCTION-2DPAGE; P00918; -.
DR UCD-2DPAGE; P00918; -.
DR PaxDb; P00918; -.
DR PeptideAtlas; P00918; -.
DR PRIDE; P00918; -.
DR DNASU; 760; -.
DR Ensembl; ENST00000285379; ENSP00000285379; ENSG00000104267.
DR GeneID; 760; -.
DR KEGG; hsa:760; -.
DR UCSC; uc003ydk.2; human.
DR CTD; 760; -.
DR GeneCards; GC08P086376; -.
DR HGNC; HGNC:1373; CA2.
DR HPA; CAB010102; -.
DR HPA; HPA001550; -.
DR MIM; 259730; phenotype.
DR MIM; 611492; gene.
DR neXtProt; NX_P00918; -.
DR Orphanet; 2785; Osteopetrosis with renal tubular acidosis.
DR PharmGKB; PA25989; -.
DR eggNOG; COG3338; -.
DR HOGENOM; HOG000112637; -.
DR HOVERGEN; HBG002837; -.
DR InParanoid; P00918; -.
DR KO; K01672; -.
DR OMA; DEANEAC; -.
DR OrthoDB; EOG7WMCK7; -.
DR BRENDA; 4.2.1.1; 2681.
DR Reactome; REACT_111217; Metabolism.
DR SABIO-RK; P00918; -.
DR ChiTaRS; CA2; human.
DR EvolutionaryTrace; P00918; -.
DR GeneWiki; Carbonic_anhydrase_II; -.
DR GenomeRNAi; 760; -.
DR NextBio; 3074; -.
DR PRO; PR:P00918; -.
DR ArrayExpress; P00918; -.
DR Bgee; P00918; -.
DR CleanEx; HS_CA2; -.
DR Genevestigator; P00918; -.
DR GO; GO:0045177; C:apical part of cell; IDA:UniProtKB.
DR GO; GO:0030424; C:axon; IEA:Ensembl.
DR GO; GO:0016323; C:basolateral plasma membrane; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IEA:Ensembl.
DR GO; GO:0005902; C:microvillus; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0004089; F:carbonate dehydratase activity; TAS:ProtInc.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0038166; P:angiotensin-mediated signaling pathway; IDA:UniProtKB.
DR GO; GO:0015701; P:bicarbonate transport; TAS:Reactome.
DR GO; GO:0015670; P:carbon dioxide transport; IEA:Ensembl.
DR GO; GO:0001822; P:kidney development; IEA:Ensembl.
DR GO; GO:0002009; P:morphogenesis of an epithelium; IEA:Ensembl.
DR GO; GO:0042475; P:odontogenesis of dentin-containing tooth; IEA:Ensembl.
DR GO; GO:0006730; P:one-carbon metabolic process; IEA:InterPro.
DR GO; GO:0045780; P:positive regulation of bone resorption; IEA:Ensembl.
DR GO; GO:0032849; P:positive regulation of cellular pH reduction; IEA:Ensembl.
DR GO; GO:2001150; P:positive regulation of dipeptide transmembrane transport; ISS:UniProtKB.
DR GO; GO:0045672; P:positive regulation of osteoclast differentiation; IEA:Ensembl.
DR GO; GO:0044070; P:regulation of anion transport; IDA:UniProtKB.
DR GO; GO:0051453; P:regulation of intracellular pH; ISS:UniProtKB.
DR GO; GO:0043627; P:response to estrogen stimulus; IEA:Ensembl.
DR GO; GO:0009268; P:response to pH; IEA:Ensembl.
DR GO; GO:0006950; P:response to stress; IEA:Ensembl.
DR GO; GO:0010043; P:response to zinc ion; IEA:Ensembl.
DR GO; GO:0046903; P:secretion; IEA:Ensembl.
DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome.
DR Gene3D; 3.10.200.10; -; 1.
DR InterPro; IPR018443; CA2/13.
DR InterPro; IPR001148; Carbonic_anhydrase_a.
DR InterPro; IPR023561; Carbonic_anhydrase_a-class.
DR InterPro; IPR018338; Carbonic_anhydrase_a-class_CS.
DR PANTHER; PTHR18952; PTHR18952; 1.
DR PANTHER; PTHR18952:SF31; PTHR18952:SF31; 1.
DR Pfam; PF00194; Carb_anhydrase; 1.
DR SMART; SM01057; Carb_anhydrase; 1.
DR SUPFAM; SSF51069; SSF51069; 1.
DR PROSITE; PS00162; ALPHA_CA_1; 1.
DR PROSITE; PS51144; ALPHA_CA_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cell membrane; Complete proteome;
KW Cytoplasm; Direct protein sequencing; Disease mutation; Lyase;
KW Membrane; Metal-binding; Osteopetrosis; Polymorphism;
KW Reference proteome; Zinc.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 260 Carbonic anhydrase 2.
FT /FTId=PRO_0000077418.
FT REGION 198 199 Substrate binding.
FT ACT_SITE 64 64
FT ACT_SITE 67 67
FT ACT_SITE 127 127
FT METAL 94 94 Zinc; catalytic.
FT METAL 96 96 Zinc; catalytic.
FT METAL 119 119 Zinc; catalytic.
FT BINDING 62 62 Activator.
FT BINDING 67 67 Activator.
FT BINDING 92 92 Activator.
FT MOD_RES 2 2 N-acetylserine.
FT VARIANT 18 18 K -> E (in Jogjakarta).
FT /FTId=VAR_001380.
FT VARIANT 92 92 Q -> P (in OPTB3; in Czechoslovakia).
FT /FTId=VAR_001381.
FT VARIANT 94 94 H -> Y (in OPTB3; partial loss of
FT activity).
FT /FTId=VAR_021009.
FT VARIANT 107 107 H -> Y (in OPTB3; frequent mutation).
FT /FTId=VAR_001382.
FT VARIANT 144 144 G -> R (in OPTB3; complete loss of
FT activity).
FT /FTId=VAR_021010.
FT VARIANT 236 236 P -> H (in Melbourne).
FT /FTId=VAR_001383.
FT VARIANT 252 252 N -> D (in dbSNP:rs2228063).
FT /FTId=VAR_001384.
FT MUTAGEN 5 5 W->A: Impaired activity, not rescued by
FT 4-methylimidazole (4-MI); when associated
FT with W-64.
FT MUTAGEN 7 7 Y->F: Enhanced activity.
FT MUTAGEN 7 7 Y->H: Reduced proton transfer rate.
FT MUTAGEN 62 62 N->A: Reduced activity.
FT MUTAGEN 62 62 N->D: Strongly reduced activity.
FT MUTAGEN 62 62 N->H: Reduced proton transfer; when
FT associated with A-64.
FT MUTAGEN 62 62 N->L: Reduced activity.
FT MUTAGEN 62 62 N->T: Reduced activity.
FT MUTAGEN 62 62 N->V: Reduced activity.
FT MUTAGEN 64 64 H->A: Reduced CO(2) hydrase activity,
FT rescued by 4-methylimidazole (4-MI).
FT Reduced proton transfer; when associated
FT with H-62. Enhanced proton transfer; when
FT associated with H-67. Enhanced proton
FT transfer capacity; when associated with
FT H-99.
FT MUTAGEN 64 64 H->G: Impaired activity, not rescued by
FT 4-methylimidazole (4-MI).
FT MUTAGEN 64 64 H->W: Impaired activity, rescued by 4-
FT methylimidazole (4-MI). Impaired
FT activity, not rescued by 4-
FT methylimidazole (4-MI); when associated
FT with A-5.
FT MUTAGEN 65 65 A->F: Reduced activity.
FT MUTAGEN 65 65 A->H,L,S: Normal activity.
FT MUTAGEN 67 67 N->H: Enhanced proton transfer; when
FT associated with A-64.
FT MUTAGEN 67 67 N->L: Reduced activity.
FT MUTAGEN 67 67 N->Q: Normal activity.
FT MUTAGEN 94 94 H->C,D,E,N,Q: Strongly reduced CO(2)
FT hydrase and p-nitrophenyl acetate
FT esterase activities, impaired stability
FT of zinc binding.
FT MUTAGEN 106 106 E->A,Q: Strongly reduced CO(2) hydrase
FT activity.
FT MUTAGEN 106 106 E->D: Normal CO(2) hydrase activity.
FT MUTAGEN 117 117 E->Q: Strongly reduced activity and
FT sulfonamide affinity.
FT MUTAGEN 119 119 H->D,N,Q: Reduced activity.
FT MUTAGEN 119 119 H->E: Strongly reduced activity.
FT MUTAGEN 121 121 V->A,G,I,L,S: Reduced CO(2) hydrase and
FT p-nitrophenyl acetate esterase
FT activities.
FT MUTAGEN 121 121 V->K,R: Strongly reduced CO(2) hydrase
FT and p-nitrophenyl acetate esterase
FT activities.
FT MUTAGEN 142 142 V->F,Y: Strongly impaired activity.
FT MUTAGEN 142 142 V->G: Weakly impaired activity.
FT MUTAGEN 142 142 V->H: Impaired activity.
FT MUTAGEN 197 197 L->A: Reduced CO(2) hydrase activity.
FT MUTAGEN 197 197 L->E,H,R: Strongly reduced CO(2) hydrase
FT activity.
FT MUTAGEN 197 197 L->F: Normal activity.
FT MUTAGEN 198 198 T->A,C,H,P: Strongly reduced activity.
FT MUTAGEN 198 198 T->D,E: Strongly reduced activity, but
FT enhanced zinc affinity.
FT MUTAGEN 198 198 T->S,V: Reduced activity.
FT MUTAGEN 199 199 T->H: Higher affinity for bicarbonate.
FT Enhanced proton transfer capacity; when
FT associated with A-64.
FT MUTAGEN 199 199 T->S: Enhanced p-nitrophenyl acetate
FT esterase activity, but normal CO(2)
FT hydrase activity.
FT MUTAGEN 201 201 P->A: Normal CO(2) hydrase activity, but
FT impaired stability.
FT CONFLICT 179 180 DP -> AA (in Ref. 6; AAH11949).
FT TURN 9 11
FT TURN 13 15
FT HELIX 16 18
FT HELIX 21 24
FT STRAND 25 27
FT STRAND 31 33
FT TURN 35 37
FT STRAND 38 40
FT STRAND 42 44
FT STRAND 45 50
FT STRAND 56 61
FT STRAND 63 70
FT STRAND 73 75
FT STRAND 77 82
FT STRAND 88 97
FT STRAND 106 109
FT STRAND 115 124
FT HELIX 125 127
FT HELIX 130 133
FT STRAND 139 151
FT HELIX 154 156
FT HELIX 157 162
FT HELIX 163 165
FT STRAND 172 174
FT HELIX 180 183
FT STRAND 190 195
FT STRAND 206 213
FT STRAND 215 217
FT HELIX 219 225
FT STRAND 229 231
FT STRAND 233 235
FT STRAND 256 258
SQ SEQUENCE 260 AA; 29246 MW; 2EC2BB7548F10558 CRC64;
MSHHWGYGKH NGPEHWHKDF PIAKGERQSP VDIDTHTAKY DPSLKPLSVS YDQATSLRIL
NNGHAFNVEF DDSQDKAVLK GGPLDGTYRL IQFHFHWGSL DGQGSEHTVD KKKYAAELHL
VHWNTKYGDF GKAVQQPDGL AVLGIFLKVG SAKPGLQKVV DVLDSIKTKG KSADFTNFDP
RGLLPESLDY WTYPGSLTTP PLLECVTWIV LKEPISVSSE QVLKFRKLNF NGEGEPEELM
VDNWRPAQPL KNRQIKASFK
//
ID CAH2_HUMAN Reviewed; 260 AA.
AC P00918; B2R7G8; Q6FI12; Q96ET9;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 180.
DE RecName: Full=Carbonic anhydrase 2;
DE EC=4.2.1.1;
DE AltName: Full=Carbonate dehydratase II;
DE AltName: Full=Carbonic anhydrase C;
DE Short=CAC;
DE AltName: Full=Carbonic anhydrase II;
DE Short=CA-II;
GN Name=CA2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3108857; DOI=10.1093/nar/15.11.4687;
RA Montgomery J.C., Venta P.J., Tashian R.E., Hewett-Emmett D.;
RT "Nucleotide sequence of human liver carbonic anhydrase II cDNA.";
RL Nucleic Acids Res. 15:4687-4687(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3121496; DOI=10.1016/0888-7543(87)90008-5;
RA Murakami H., Marelich G.P., Grubb J.H., Kyle J.W., Sly W.S.;
RT "Cloning, expression, and sequence homologies of cDNA for human
RT carbonic anhydrase II.";
RL Genomics 1:159-166(1987).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S.,
RA Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W.,
RA Korn B., Zuo D., Hu Y., LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Urinary bladder;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ovary;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PROTEIN SEQUENCE OF 2-260.
RX PubMed=4207120;
RA Lin K.-T.D., Deutsch H.F.;
RT "Human carbonic anhydrases. XII. The complete primary structure of the
RT C isozyme.";
RL J. Biol. Chem. 249:2329-2337(1974).
RN [8]
RP PROTEIN SEQUENCE OF 2-260.
RX PubMed=823150;
RA Henderson L.E., Henriksson D., Nyman P.O.;
RT "Primary structure of human carbonic anhydrase C.";
RL J. Biol. Chem. 251:5457-5463(1976).
RN [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-77.
RX PubMed=3000449; DOI=10.1016/0167-4781(85)90006-5;
RA Venta P.J., Montgomery J.C., Hewett-Emmett D., Tashian R.E.;
RT "Comparison of the 5' regions of human and mouse carbonic anhydrase II
RT genes and identification of possible regulatory elements.";
RL Biochim. Biophys. Acta 826:195-201(1985).
RN [10]
RP INTERACTION WITH SLC4A4.
RX PubMed=14567693; DOI=10.1021/bi0353124;
RA Alvarez B.V., Loiselle F.B., Supuran C.T., Schwartz G.J., Casey J.R.;
RT "Direct extracellular interaction between carbonic anhydrase IV and
RT the human NBC1 sodium/bicarbonate co-transporter.";
RL Biochemistry 42:12321-12329(2003).
RN [11]
RP INTERACTION WITH SLC4A7.
RX PubMed=14736710; DOI=10.1152/ajpcell.00382.2003;
RA Loiselle F.B., Morgan P.E., Alvarez B.V., Casey J.R.;
RT "Regulation of the human NBC3 Na+/HCO3- cotransporter by carbonic
RT anhydrase II and PKA.";
RL Am. J. Physiol. 286:C1423-C1433(2004).
RN [12]
RP INTERACTION WITH SLC4A4.
RX PubMed=15218065; DOI=10.1113/jphysiol.2004.065110;
RA Pushkin A., Abuladze N., Gross E., Newman D., Tatishchev S., Lee I.,
RA Fedotoff O., Bondar G., Azimov R., Ngyuen M., Kurtz I.;
RT "Molecular mechanism of kNBC1-carbonic anhydrase II interaction in
RT proximal tubule cells.";
RL J. Physiol. (Lond.) 559:55-65(2004).
RN [13]
RP FUNCTION, INTERACTION WITH SLC26A6, AND SUBCELLULAR LOCATION.
RX PubMed=15990874; DOI=10.1038/sj.emboj.7600736;
RA Alvarez B.V., Vilas G.L., Casey J.R.;
RT "Metabolon disruption: a mechanism that regulates bicarbonate
RT transport.";
RL EMBO J. 24:2499-2511(2005).
RN [14]
RP ENZYME REGULATION.
RX PubMed=17314045; DOI=10.1016/j.bmcl.2007.01.113;
RA Temperini C., Innocenti A., Guerri A., Scozzafava A., Rusconi S.,
RA Supuran C.T.;
RT "Phosph(on)ate as a zinc-binding group in metalloenzyme inhibitors: X-
RT ray crystal structure of the antiviral drug foscarnet complexed to
RT human carbonic anhydrase I.";
RL Bioorg. Med. Chem. Lett. 17:2210-2215(2007).
RN [15]
RP BIOPHYSICOCHEMICAL PROPERTIES, AND ENZYME REGULATION.
RX PubMed=18618712; DOI=10.1002/prot.22144;
RA Di Fiore A., Monti S.M., Hilvo M., Parkkila S., Romano V., Scaloni A.,
RA Pedone C., Scozzafava A., Supuran C.T., De Simone G.;
RT "Crystal structure of human carbonic anhydrase XIII and its complex
RT with the inhibitor acetazolamide.";
RL Proteins 74:164-175(2009).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
RX PubMed=4621826;
RA Liljas A., Kannan K.K., Bergsten P.-C., Waara I., Fridborg K.,
RA Strandberg B., Carlbom U., Jaerup L., Loevgren S., Petef M.;
RT "Crystal structure of human carbonic anhydrase C.";
RL Nature New Biol. 235:131-137(1972).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) IN COMPLEX WITH ZINC ION.
RX PubMed=3151019; DOI=10.1002/prot.340040406;
RA Eriksson A.E., Jones T.A., Liljas A.;
RT "Refined structure of human carbonic anhydrase II at 2.0-A
RT resolution.";
RL Proteins 4:274-282(1988).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) IN COMPLEX WITH ZINC ION AND
RP INHIBITORS.
RX PubMed=3151020; DOI=10.1002/prot.340040407;
RA Eriksson A.E., Kylsten P.M., Jones T.A., Liljas A.;
RT "Crystallographic studies of inhibitor binding sites in human carbonic
RT anhydrase II: a pentacoordinated binding of the SCN-ion to the zinc at
RT high pH.";
RL Proteins 4:283-293(1988).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF MUTANT SER-199 IN COMPLEX
RP WITH ZINC ION, MUTAGENESIS OF THR-199, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=1909891; DOI=10.1021/bi00102a005;
RA Krebs J.F., Fierke C.A., Alexander R.S., Christianson D.W.;
RT "Conformational mobility of His-64 in the Thr-200TO: human carbonic
RT anhydrase II.";
RL Biochemistry 30:9153-9160(1991).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF MUTANTS PHE-142; TYR-142 AND
RP HIS-142 IN COMPLEX WITH INHIBITORS, AND MUTAGENESIS OF VAL-142.
RX PubMed=1932029; DOI=10.1021/bi00110a008;
RA Alexander R.S., Nair S.K., Christianson D.W.;
RT "Engineering the hydrophobic pocket of carbonic anhydrase II.";
RL Biochemistry 30:11064-11072(1991).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF MUTANT ALA-121, MUTAGENESIS
RP OF VAL-121, ENZYME REGULATION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=1910042;
RA Nair S.K., Calderone T.L., Christianson D.W., Fierke C.A.;
RT "Altering the mouth of a hydrophobic pocket. Structure and kinetics of
RT human carbonic anhydrase II mutants at residue Val-121.";
RL J. Biol. Chem. 266:17320-17325(1991).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) IN COMPLEX WITH ZINC ION AND
RP INHIBITORS, AND ENZYME REGULATION.
RX PubMed=1336460; DOI=10.1111/j.1432-1033.1992.tb17490.x;
RA Mangani S., Haakansson K.;
RT "Crystallographic studies of the binding of protonated and
RT unprotonated inhibitors to carbonic anhydrase using hydrogen sulphide
RT and nitrate anions.";
RL Eur. J. Biochem. 210:867-871(1992).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (1.54 ANGSTROMS) IN COMPLEX WITH ZINC ION AND
RP INHIBITORS.
RX PubMed=1433293; DOI=10.1016/0022-2836(92)90531-N;
RA Haakansson K., Carlsson M., Svensson L.A., Liljas A.;
RT "Structure of native and apo carbonic anhydrase II and structure of
RT some of its anion-ligand complexes.";
RL J. Mol. Biol. 227:1192-1204(1992).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (1.88 ANGSTROMS) IN COMPLEX WITH COBALT ION AND
RP BICARBONATE.
RX PubMed=1474587; DOI=10.1016/0022-2836(92)90327-G;
RA Haakansson K., Wehnert A.;
RT "Structure of cobalt carbonic anhydrase complexed with bicarbonate.";
RL J. Mol. Biol. 228:1212-1218(1992).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF MUTANT CYS-94 IN COMPLEX
RP WITH ZINC ION, AND MUTAGENESIS OF HIS-94.
RX PubMed=8431430; DOI=10.1021/bi00057a015;
RA Alexander R.S., Kiefer L.L., Fierke C.A., Christianson D.W.;
RT "Engineering the zinc binding site of human carbonic anhydrase II:
RT structure of the His-94-->Cys apoenzyme in a new crystalline form.";
RL Biochemistry 32:1510-1518(1993).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF MUTANT ALA-197; GLU-197;
RP HIS-197 AND ARG-197, AND MUTAGENESIS OF LEU-197.
RX PubMed=8485129; DOI=10.1021/bi00068a005;
RA Nair S.K., Christianson D.W.;
RT "Structural consequences of hydrophilic amino acid substitutions in
RT the hydrophobic pocket of human carbonic anhydrase II.";
RL Biochemistry 32:4506-4514(1993).
RN [28]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF MUTANT CYS-198 IN COMPLEX
RP WITH ZINC ION, AND MUTAGENESIS OF THR-198.
RX PubMed=8399159; DOI=10.1021/bi00089a005;
RA Ippolito J.A., Christianson D.W.;
RT "Structure of an engineered His3Cys zinc binding site in human
RT carbonic anhydrase II.";
RL Biochemistry 32:9901-9905(1993).
RN [29]
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF MUTANT ALA-201 IN COMPLEX
RP WITH ZINC ION, AND MUTAGENESIS OF PRO-201.
RX PubMed=8218160; DOI=10.1021/bi00092a003;
RA Tweedy N.B., Nair S.K., Paterno S.A., Fierke C.A., Christianson D.W.;
RT "Structure and energetics of a non-proline cis-peptidyl linkage in a
RT proline-202-->alanine carbonic anhydrase II variant.";
RL Biochemistry 32:10944-10949(1993).
RN [30]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) IN COMPLEX WITH ZINC ION AND
RP INHIBITORS.
RX PubMed=8482389; DOI=10.1016/0014-5793(93)81565-H;
RA Joensson B.M., Haakansson K., Liljas A.;
RT "The structure of human carbonic anhydrase II in complex with bromide
RT and azide.";
RL FEBS Lett. 322:186-190(1993).
RN [31]
RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF MUTANT VAL-198 IN COMPLEX
RP WITH ZINC ION AND INHIBITORS, MUTAGENESIS OF THR-198, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=8262987;
RA Krebs J.F., Ippolito J.A., Christianson D.W., Fierke C.A.;
RT "Structural and functional importance of a conserved hydrogen bond
RT network in human carbonic anhydrase II.";
RL J. Biol. Chem. 268:27458-27466(1993).
RN [32]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) IN COMPLEX WITH INHIBITOR AND
RP ZINC ION.
RX PubMed=8331673; DOI=10.1006/jmbi.1993.1365;
RA Mangani S., Liljas A.;
RT "Crystal structure of the complex between human carbonic anhydrase II
RT and the aromatic inhibitor 1,2,4-triazole.";
RL J. Mol. Biol. 232:9-14(1993).
RN [33]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF MUTANT HIS-199 IN COMPLEX
RP WITH BICARBONATE AND ZINC ION, AND MUTAGENESIS OF THR-199.
RX PubMed=8451242; DOI=10.1002/prot.340150110;
RA Xue Y., Vidgren J., Svensson L.A., Liljas A., Jonsson B.H.,
RA Lindskog S.;
RT "Crystallographic analysis of Thr-200-->His human carbonic anhydrase
RT II and its complex with the substrate, HCO3-.";
RL Proteins 15:80-87(1993).
RN [34]
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF MUTANTS IN COMPLEX WITH
RP BICARBONATE AND ZINC ION, AND MUTAGENESIS OF GLU-106 AND THR-198.
RX PubMed=7901850; DOI=10.1002/prot.340170112;
RA Xue Y., Liljas A., Jonsson B.H., Lindskog S.;
RT "Structural analysis of the zinc hydroxide-Thr-199-Glu-106 hydrogen-
RT bond network in human carbonic anhydrase II.";
RL Proteins 17:93-106(1993).
RN [35]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) IN COMPLEX WITH COBALT; COPPER;
RP NICKEL AND MANGANESE IONS.
RX PubMed=15299481; DOI=10.1107/S0907444993008790;
RA Haakansson K., Wehnert A., Liljas A.;
RT "X-ray analysis of metal-substituted human carbonic anhydrase II
RT derivatives.";
RL Acta Crystallogr. D 50:93-100(1994).
RN [36]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) MUTANT GLN-106 IN COMPLEX WITH
RP THE INHIBITOR ACETATE, AND MUTAGENESIS OF GLU-106.
RX PubMed=15299482; DOI=10.1107/S0907444993009667;
RA Haakansson K., Briand C., Zaitsev V., Xue Y., Liljas A.;
RT "Wild-type and E106Q mutant carbonic anhydrase complexed with
RT acetate.";
RL Acta Crystallogr. D 50:101-104(1994).
RN [37]
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 2-259 OF MUTANTS ALA-94;
RP CYS-94; CYS-96; CYS-119 AND ASP-119 IN COMPLEX WITH ZINC ION.
RX PubMed=7803386; DOI=10.1021/bi00255a004;
RA Ippolito J.A., Christianson D.W.;
RT "Structural consequences of redesigning a protein-zinc binding site.";
RL Biochemistry 33:15241-15249(1994).
RN [38]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) IN COMPLEX WITH THE INHIBITOR
RP TRIFLUOROMETHANE SULPHONAMIDE.
RX PubMed=8070585; DOI=10.1016/0014-5793(94)00798-5;
RA Haakansson K., Liljas A.;
RT "The structure of a complex between carbonic anhydrase II and a new
RT inhibitor, trifluoromethane sulphonamide.";
RL FEBS Lett. 350:319-322(1994).
RN [39]
RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) IN COMPLEX WITH INHIBITORS.
RX PubMed=8142888; DOI=10.1002/pro.5560030115;
RA Smith G.M., Alexander R.S., Christianson D.W., McKeever B.M.,
RA Ponticello G.S., Springer J.P., Randall W.C., Baldwin J.J.,
RA Habecker C.N.;
RT "Positions of His-64 and a bound water in human carbonic anhydrase II
RT upon binding three structurally related inhibitors.";
RL Protein Sci. 3:118-125(1994).
RN [40]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF MUTANTS ARG-197; ASP-197 AND
RP PHE-197 IN COMPLEX WITH THE INHIBITOR ACETAZOLAMIDE.
RX PubMed=7696263; DOI=10.1021/bi00012a016;
RA Nair S.K., Krebs J.F., Christianson D.W., Fierke C.A.;
RT "Structural basis of inhibitor affinity to variants of human carbonic
RT anhydrase II.";
RL Biochemistry 34:3981-3989(1995).
RN [41]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) IN COMPLEX WITH INHIBITORS.
RX PubMed=7608893; DOI=10.1021/jm00013a004;
RA Boriack P.A., Christianson D.W., Kingery-Wood J., Whitesides G.M.;
RT "Secondary interactions significantly removed from the sulfonamide
RT binding pocket of carbonic anhydrase II influence inhibitor binding
RT constants.";
RL J. Med. Chem. 38:2286-2291(1995).
RN [42]
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF MUTANTS ASP-198; GLU-198 AND
RP HIS-198 IN COMPLEX WITH ZINC ION, MUTAGENESIS OF THR-198, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=7761440; DOI=10.1073/pnas.92.11.5017;
RA Ippolito J.A., Baird T.T. Jr., McGee S.A., Christianson D.W.,
RA Fierke C.A.;
RT "Structure-assisted redesign of a protein-zinc-binding site with
RT femtomolar affinity.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:5017-5021(1995).
RN [43]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF THE MUTANT GLN-117 IN
RP COMPLEX WITH ZINC ION AND THE INHIBITOR ACETAZOLAMIDE, AND MUTAGENESIS
RP OF GLU-117.
RX PubMed=8639494; DOI=10.1021/bi9526692;
RA Huang C.C., Lesburg C.A., Kiefer L.L., Fierke C.A., Christianson D.W.;
RT "Reversal of the hydrogen bond to zinc ligand histidine-119
RT dramatically diminishes catalysis and enhances metal equilibration
RT kinetics in carbonic anhydrase II.";
RL Biochemistry 35:3439-3446(1996).
RN [44]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF MUTANTS GLY-65; HIS-65;
RP LEU-65; PHE-65; SER-65 AND THR-65 IN COMPLEX WITH ZINC ION.
RX PubMed=8987974; DOI=10.1021/bi9617872;
RA Scolnick L.R., Christianson D.W.;
RT "X-ray crystallographic studies of alanine-65 variants of carbonic
RT anhydrase II reveal the structural basis of compromised proton
RT transfer in catalysis.";
RL Biochemistry 35:16429-16434(1996).
RN [45]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) IN COMPLEX WITH THE INHIBITOR
RP DANSYLAMIDE.
RX PubMed=8557623;
RA Nair S.K., Elbaum D., Christianson D.W.;
RT "Unexpected binding mode of the sulfonamide fluorophore 5-
RT dimethylamino-1-naphthalene sulfonamide to human carbonic anhydrase
RT II. Implications for the development of a zinc biosensor.";
RL J. Biol. Chem. 271:1003-1007(1996).
RN [46]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) IN COMPLEX WITH THE ACTIVATOR
RP HISTAMINE, AND ENZYME REGULATION.
RX PubMed=9265618; DOI=10.1021/bi970760v;
RA Briganti F., Mangani S., Orioli P., Scozzafava A., Vernaglione G.,
RA Supuran C.T.;
RT "Carbonic anhydrase activators: X-ray crystallographic and
RT spectroscopic investigations for the interaction of isozymes I and II
RT with histamine.";
RL Biochemistry 36:10384-10392(1997).
RN [47]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF MUTANTS ASN-94; ASN-119 AND
RP GLN-119 IN COMPLEX WITH ZINC ION, MUTAGENESIS OF HIS-94 AND HIS-119,
RP AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=9398308; DOI=10.1021/bi971296x;
RA Lesburg C.A., Huang C., Christianson D.W., Fierke C.A.;
RT "Histidine --> carboxamide ligand substitutions in the zinc binding
RT site of carbonic anhydrase II alter metal coordination geometry but
RT retain catalytic activity.";
RL Biochemistry 36:15780-15791(1997).
RN [48]
RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) IN COMPLEX WITH THE INHIBITOR
RP BRINZOLAMIDE.
RX PubMed=9541386;
RA Stams T., Chen Y., Boriack-Sjodin P.A., Hurt J.D., Liao J., May J.A.,
RA Dean T., Laipis P., Silverman D.N., Christianson D.W.;
RT "Structures of murine carbonic anhydrase IV and human carbonic
RT anhydrase II complexed with brinzolamide: molecular basis of isozyme-
RT drug discrimination.";
RL Protein Sci. 7:556-563(1998).
RN [49]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) IN COMPLEX WITH SULFONAMIDE
RP INHIBITORS AND ZINC ION.
RX PubMed=9865942; DOI=10.1002/pro.5560071201;
RA Boriack-Sjodin P.A., Zeitlin S., Chen H.H., Crenshaw L., Gross S.,
RA Dantanarayana A., Delgado P., May J.A., Dean T., Christianson D.W.;
RT "Structural analysis of inhibitor binding to human carbonic anhydrase
RT II.";
RL Protein Sci. 7:2483-2489(1998).
RN [50]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) IN COMPLEX WITH CYANAMIDE AND
RP SUBSTRATE, FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=10550681; DOI=10.1007/s007750050375;
RA Briganti F., Mangani S., Scozzafava A., Vernaglione G., Supuran C.T.;
RT "Carbonic anhydrase catalyzes cyanamide hydration to urea: is it
RT mimicking the physiological reaction?";
RL J. Biol. Inorg. Chem. 4:528-536(1999).
RN [51]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) IN COMPLEX WITH CYANAMIDE.
RX PubMed=11015219; DOI=10.1021/bi000937c;
RA Guerri A., Briganti F., Scozzafava A., Supuran C.T., Mangani S.;
RT "Mechanism of cyanamide hydration catalyzed by carbonic anhydrase II
RT suggested by cryogenic X-ray diffraction.";
RL Biochemistry 39:12391-12397(2000).
RN [52]
RP X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) OF MUTANTS ILE-93/MET-95/VAL-97
RP AND SER-93/LEU-95/MET-97 IN COMPLEX WITH COBALT; COPPER AND ZINC IONS.
RX PubMed=11076507; DOI=10.1021/bi001649j;
RA Cox J.D., Hunt J.A., Compher K.M., Fierke C.A., Christianson D.W.;
RT "Structural influence of hydrophobic core residues on metal binding
RT and specificity in carbonic anhydrase II.";
RL Biochemistry 39:13687-13694(2000).
RN [53]
RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF THE MUTANT ALA-64 IN COMPLEX
RP WITH 4-METHYLIMIDAZOLE, AND MUTAGENESIS OF HIS-64.
RX PubMed=11327835; DOI=10.1021/bi002295z;
RA Duda D., Tu C., Qian M., Laipis P., Agbandje-McKenna M.,
RA Silverman D.N., McKenna R.;
RT "Structural and kinetic analysis of the chemical rescue of the proton
RT transfer function of carbonic anhydrase II.";
RL Biochemistry 40:1741-1748(2001).
RN [54]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF MUTANT VAL-130 IN COMPLEX
RP WITH FLUOROAROMATIC INHIBITORS.
RX PubMed=11572683; DOI=10.1021/ja011034p;
RA Kim C.Y., Chandra P.P., Jain A., Christianson D.W.;
RT "Fluoroaromatic-fluoroaromatic interactions between inhibitors bound
RT in the crystal lattice of human carbonic anhydrase II.";
RL J. Am. Chem. Soc. 123:9620-9627(2001).
RN [55]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) IN COMPLEX WITH THE INHIBITOR
RP SUGAR SULFAMATE RWJ-37497, AND ENZYME REGULATION.
RX PubMed=11802772; DOI=10.1042/0264-6021:3610437;
RA Recacha R., Costanzo M.J., Maryanoff B.E., Chattopadhyay D.;
RT "Crystal structure of human carbonic anhydrase II complexed with an
RT anti-convulsant sugar sulphamate.";
RL Biochem. J. 361:437-441(2002).
RN [56]
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF THE MUTANT PRO-198/SER-205
RP IN COMPLEX WITH BICARBONATE AND INHIBITORS, AND MUTAGENESIS OF
RP THR-198.
RX PubMed=12056894; DOI=10.1021/bi020053o;
RA Huang S., Sjoeblom B., Sauer-Eriksson A.E., Jonsson B.H.;
RT "Organization of an efficient carbonic anhydrase: implications for the
RT mechanism based on structure-function studies of a T199P/C206S
RT mutant.";
RL Biochemistry 41:7628-7635(2002).
RN [57]
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF THE MUTANT HIS-7, AND
RP MUTAGENESIS OF TYR-7.
RX PubMed=12171926; DOI=10.1074/jbc.M205791200;
RA Tu C., Qian M., An H., Wadhwa N.R., Duda D., Yoshioka C., Pathak Y.,
RA McKenna R., Laipis P.J., Silverman D.N.;
RT "Kinetic analysis of multiple proton shuttles in the active site of
RT human carbonic anhydrase.";
RL J. Biol. Chem. 277:38870-38876(2002).
RN [58]
RP X-RAY CRYSTALLOGRAPHY (1.93 ANGSTROMS) IN COMPLEX WITH INHIBITORS, AND
RP FUNCTION.
RX PubMed=11831900; DOI=10.1021/jm010163d;
RA Kim C.Y., Whittington D.A., Chang J.S., Liao J., May J.A.,
RA Christianson D.W.;
RT "Structural aspects of isozyme selectivity in the binding of
RT inhibitors to carbonic anhydrases II and IV.";
RL J. Med. Chem. 45:888-893(2002).
RN [59]
RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) IN COMPLEX WITH INHIBITORS.
RX PubMed=12166932; DOI=10.1021/jm011112j;
RA Grueneberg S., Stubbs M.T., Klebe G.;
RT "Successful virtual screening for novel inhibitors of human carbonic
RT anhydrase: strategy and experimental confirmation.";
RL J. Med. Chem. 45:3588-3602(2002).
RN [60]
RP X-RAY CRYSTALLOGRAPHY (1.94 ANGSTROMS) IN COMPLEX WITH INHIBITORS.
RX PubMed=11818565; DOI=10.1073/pnas.032673399;
RA Grzybowski B.A., Ishchenko A.V., Kim C.Y., Topalov G., Chapman R.,
RA Christianson D.W., Whitesides G.M., Shakhnovich E.I.;
RT "Combinatorial computational method gives new picomolar ligands for a
RT known enzyme.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:1270-1273(2002).
RN [61]
RP X-RAY CRYSTALLOGRAPHY (1.05 ANGSTROMS) OF THE MUTANT ALA-64 IN COMPLEX
RP WITH THE INHIBITOR 4-METHYLIMIDAZOLE AND ZINC ION.
RX PubMed=12499545;
RA Duda D., Govindasamy L., Agbandje-McKenna M., Tu C., Silverman D.N.,
RA McKenna R.;
RT "The refined atomic structure of carbonic anhydrase II at 1.05 A
RT resolution: implications of chemical rescue of proton transfer.";
RL Acta Crystallogr. D 59:93-104(2003).
RN [62]
RP X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) IN COMPLEX WITH INHIBITORS, AND
RP ENZYME REGULATION.
RX PubMed=14736236; DOI=10.1021/jm030912m;
RA Weber A., Casini A., Heine A., Kuhn D., Supuran C.T., Scozzafava A.,
RA Klebe G.;
RT "Unexpected nanomolar inhibition of carbonic anhydrase by COX-2-
RT selective celecoxib: new pharmacological opportunities due to related
RT binding site recognition.";
RL J. Med. Chem. 47:550-557(2004).
RN [63]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) IN COMPLEX WITH THE ANTI-CANCER
RP AGENT 667-COUMATE.
RX PubMed=15453828; DOI=10.1042/BJ20041037;
RA Lloyd M.D., Pederick R.L., Natesh R., Woo L.W., Purohit A., Reed M.J.,
RA Acharya K.R., Potter B.V.;
RT "Crystal structure of human carbonic anhydrase II at 1.95 A resolution
RT in complex with 667-coumate, a novel anti-cancer agent.";
RL Biochem. J. 385:715-720(2005).
RN [64]
RP X-RAY CRYSTALLOGRAPHY (1.63 ANGSTROMS), MUTAGENESIS OF ASN-62; HIS-64
RP AND ASN-67, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=15667203; DOI=10.1021/bi0480279;
RA Fisher Z., Hernandez Prada J.A., Tu C., Duda D., Yoshioka C., An H.,
RA Govindasamy L., Silverman D.N., McKenna R.;
RT "Structural and kinetic characterization of active-site histidine as a
RT proton shuttle in catalysis by human carbonic anhydrase II.";
RL Biochemistry 44:1097-1105(2005).
RN [65]
RP X-RAY CRYSTALLOGRAPHY (1.76 ANGSTROMS) IN COMPLEX WITH DUAL
RP AROMATASE-STEROID SULFATASE INHIBITORS.
RX PubMed=15865431; DOI=10.1021/bi047692e;
RA Lloyd M.D., Thiyagarajan N., Ho Y.T., Woo L.W., Sutcliffe O.B.,
RA Purohit A., Reed M.J., Acharya K.R., Potter B.V.;
RT "First crystal structures of human carbonic anhydrase II in complex
RT with dual aromatase-steroid sulfatase inhibitors.";
RL Biochemistry 44:6858-6866(2005).
RN [66]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) IN COMPLEX WITH ACTIVATOR
RP L-HISTIDINE, AND ENZYME REGULATION.
RX PubMed=16214338; DOI=10.1016/j.bmcl.2005.08.069;
RA Temperini C., Scozzafava A., Puccetti L., Supuran C.T.;
RT "Carbonic anhydrase activators: X-ray crystal structure of the adduct
RT of human isozyme II with L-histidine as a platform for the design of
RT stronger activators.";
RL Bioorg. Med. Chem. Lett. 15:5136-5141(2005).
RN [67]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) IN COMPLEX WITH INHIBITOR.
RX PubMed=16134940; DOI=10.1021/jm050333c;
RA Menchise V., De Simone G., Alterio V., Di Fiore A., Pedone C.,
RA Scozzafava A., Supuran C.T.;
RT "Carbonic anhydrase inhibitors: stacking with Phe131 determines active
RT site binding region of inhibitors as exemplified by the X-ray crystal
RT structure of a membrane-impermeant antitumor sulfonamide complexed
RT with isozyme II.";
RL J. Med. Chem. 48:5721-5727(2005).
RN [68]
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS), AND MUTAGENESIS OF HIS-64 AND
RP THR-199.
RX PubMed=16106378; DOI=10.1002/prot.20615;
RA Bhatt D., Tu C., Fisher S.Z., Hernandez Prada J.A., McKenna R.,
RA Silverman D.N.;
RT "Proton transfer in a Thr200His mutant of human carbonic anhydrase
RT II.";
RL Proteins 61:239-245(2005).
RN [69]
RP X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS).
RX PubMed=16511248; DOI=10.1107/S1744309105038248;
RA Budayova-Spano M., Fisher S.Z., Dauvergne M.T., Agbandje-McKenna M.,
RA Silverman D.N., Myles D.A., McKenna R.;
RT "Production and X-ray crystallographic analysis of fully deuterated
RT human carbonic anhydrase II.";
RL Acta Crystallogr. F 62:6-9(2006).
RN [70]
RP X-RAY CRYSTALLOGRAPHY (1.15 ANGSTROMS) IN COMPLEX WITH INHIBITORS.
RX PubMed=16820676; DOI=10.1107/S1744309106020446;
RA Fisher S.Z., Govindasamy L., Boyle N., Agbandje-McKenna M.,
RA Silverman D.N., Blackburn G.M., McKenna R.;
RT "X-ray crystallographic studies reveal that the incorporation of
RT spacer groups in carbonic anhydrase inhibitors causes alternate
RT binding modes.";
RL Acta Crystallogr. F 62:618-622(2006).
RN [71]
RP X-RAY CRYSTALLOGRAPHY (1.46 ANGSTROMS) IN COMPLEX WITH INHIBITORS
RP VALDECOXIB AND CELECOXIB, AND ENZYME REGULATION.
RX PubMed=16290146; DOI=10.1016/j.bmcl.2005.09.040;
RA Di Fiore A., Pedone C., D'Ambrosio K., Scozzafava A., De Simone G.,
RA Supuran C.T.;
RT "Carbonic anhydrase inhibitors: Valdecoxib binds to a different active
RT site region of the human isoform II as compared to the structurally
RT related cyclooxygenase II 'selective' inhibitor celecoxib.";
RL Bioorg. Med. Chem. Lett. 16:437-442(2006).
RN [72]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) IN COMPLEX WITH N-HYDROXYUREA,
RP AND ENZYME REGULATION.
RX PubMed=16759856; DOI=10.1016/j.bmcl.2006.05.068;
RA Temperini C., Innocenti A., Scozzafava A., Supuran C.T.;
RT "N-hydroxyurea -- a versatile zinc binding function in the design of
RT metalloenzyme inhibitors.";
RL Bioorg. Med. Chem. Lett. 16:4316-4320(2006).
RN [73]
RP X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) IN COMPLEX WITH INHIBITORS.
RX PubMed=17000110; DOI=10.1016/j.bmcl.2006.09.022;
RA Menchise V., De Simone G., Di Fiore A., Scozzafava A., Supuran C.T.;
RT "Carbonic anhydrase inhibitors: X-ray crystallographic studies for the
RT binding of 5-amino-1,3,4-thiadiazole-2-sulfonamide and 5-(4-amino-3-
RT chloro-5-fluorophenylsulfonamido)-1,3,4-thiadiazole-2-sulfonamide to
RT human isoform II.";
RL Bioorg. Med. Chem. Lett. 16:6204-6208(2006).
RN [74]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) IN COMPLEX WITH L- AND
RP D-HISTIDINE, AND ENZYME REGULATION.
RX PubMed=16807956; DOI=10.1002/chem.200600159;
RA Temperini C., Scozzafava A., Vullo D., Supuran C.T.;
RT "Carbonic anhydrase activators. Activation of isozymes I, II, IV, VA,
RT VII, and XIV with l- and d-histidine and crystallographic analysis of
RT their adducts with isoform II: engineering proton-transfer processes
RT within the active site of an enzyme.";
RL Chemistry 12:7057-7066(2006).
RN [75]
RP X-RAY CRYSTALLOGRAPHY (0.99 ANGSTROMS) IN COMPLEX WITH TWO-PRONG
RP INHIBITORS.
RX PubMed=16506782; DOI=10.1021/ja057257n;
RA Jude K.M., Banerjee A.L., Haldar M.K., Manokaran S., Roy B.,
RA Mallik S., Srivastava D.K., Christianson D.W.;
RT "Ultrahigh resolution crystal structures of human carbonic anhydrases
RT I and II complexed with 'two-prong' inhibitors reveal the molecular
RT basis of high affinity.";
RL J. Am. Chem. Soc. 128:3011-3018(2006).
RN [76]
RP X-RAY CRYSTALLOGRAPHY (1.71 ANGSTROMS) IN COMPLEX WITH INHIBITOR.
RX PubMed=16787097; DOI=10.1021/ja061574s;
RA Alterio V., Vitale R.M., Monti S.M., Pedone C., Scozzafava A.,
RA Cecchi A., De Simone G., Supuran C.T.;
RT "Carbonic anhydrase inhibitors: X-ray and molecular modeling study for
RT the interaction of a fluorescent antitumor sulfonamide with isozyme II
RT and IX.";
RL J. Am. Chem. Soc. 128:8329-8335(2006).
RN [77]
RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) IN COMPLEX WITH L- AND
RP D-PHENYLALANINE, AND ENZYME REGULATION.
RX PubMed=16686544; DOI=10.1021/jm0603320;
RA Temperini C., Scozzafava A., Vullo D., Supuran C.T.;
RT "Carbonic anhydrase activators. Activation of isoforms I, II, IV, VA,
RT VII, and XIV with L- and D-phenylalanine and crystallographic analysis
RT of their adducts with isozyme II: stereospecific recognition within
RT the active site of an enzyme and its consequences for the drug
RT design.";
RL J. Med. Chem. 49:3019-3027(2006).
RN [78]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) IN COMPLEX WITH INHIBITOR.
RX PubMed=16942027; DOI=10.1021/jm060531j;
RA De Simone G., Vitale R.M., Di Fiore A., Pedone C., Scozzafava A.,
RA Montero J.-L., Winum J.-Y., Supuran C.T.;
RT "Carbonic anhydrase inhibitors: Hypoxia-activatable sulfonamides
RT incorporating disulfide bonds that target the tumor-associated isoform
RT IX.";
RL J. Med. Chem. 49:5544-5551(2006).
RN [79]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) IN COMPLEX WITH INHIBITOR.
RX PubMed=17125255; DOI=10.1021/jm060807n;
RA Winum J.Y., Temperini C., El Cheikh K., Innocenti A., Vullo D.,
RA Ciattini S., Montero J.-L., Scozzafava A., Supuran C.T.;
RT "Carbonic anhydrase inhibitors: clash with Ala65 as a means for
RT designing inhibitors with low affinity for the ubiquitous isozyme II,
RT exemplified by the crystal structure of the topiramate sulfamide
RT analogue.";
RL J. Med. Chem. 49:7024-7031(2006).
RN [80]
RP X-RAY CRYSTALLOGRAPHY (1.46 ANGSTROMS) IN COMPLEX WITH INHIBITORS.
RX PubMed=17181151; DOI=10.1021/jm060705x;
RA Leese M.P., Leblond B., Smith A., Newman S.P., Di Fiore A.,
RA De Simone G., Supuran C.T., Purohit A., Reed M.J., Potter B.V.;
RT "2-substituted estradiol bis-sulfamates, multitargeted antitumor
RT agents: synthesis, in vitro SAR, protein crystallography, and in vivo
RT activity.";
RL J. Med. Chem. 49:7683-7696(2006).
RN [81]
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) IN COMPLEX WITH SACCHARIN, AND
RP ENZYME REGULATION.
RX PubMed=17705204; DOI=10.1002/anie.200701189;
RA Koehler K., Hillebrecht A., Schulze Wischeler J., Innocenti A.,
RA Heine A., Supuran C.T., Klebe G.;
RT "Saccharin inhibits carbonic anhydrases: possible explanation for its
RT unpleasant metallic aftertaste.";
RL Angew. Chem. Int. Ed. Engl. 46:7697-7699(2007).
RN [82]
RP X-RAY CRYSTALLOGRAPHY (1.05 ANGSTROMS).
RX PubMed=17319692; DOI=10.1021/bi062066y;
RA Fisher S.Z., Maupin C.M., Budayova-Spano M., Govindasamy L., Tu C.,
RA Agbandje-McKenna M., Silverman D.N., Voth G.A., McKenna R.;
RT "Atomic crystal and molecular dynamics simulation structures of human
RT carbonic anhydrase II: insights into the proton transfer mechanism.";
RL Biochemistry 46:2930-2937(2007).
RN [83]
RP X-RAY CRYSTALLOGRAPHY (1.15 ANGSTROMS), MUTAGENESIS OF TYR-7; ASN-62
RP AND ASN-67, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=17330962; DOI=10.1021/bi602620k;
RA Fisher S.Z., Tu C., Bhatt D., Govindasamy L., Agbandje-McKenna M.,
RA McKenna R., Silverman D.N.;
RT "Speeding up proton transfer in a fast enzyme: kinetic and
RT crystallographic studies on the effect of hydrophobic amino acid
RT substitutions in the active site of human carbonic anhydrase II.";
RL Biochemistry 46:3803-3813(2007).
RN [84]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) IN COMPLEX WITH ACTIVATOR
RP L-ADRENALINE, AND ENZYME REGULATION.
RX PubMed=17127057; DOI=10.1016/j.bmcl.2006.11.027;
RA Temperini C., Innocenti A., Scozzafava A., Mastrolorenzo A.,
RA Supuran C.T.;
RT "Carbonic anhydrase activators: L-Adrenaline plugs the active site
RT entrance of isozyme II, activating better isoforms I, IV, VA, VII, and
RT XIV.";
RL Bioorg. Med. Chem. Lett. 17:628-635(2007).
RN [85]
RP X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) IN COMPLEX WITH INHIBITOR.
RX PubMed=17251017; DOI=10.1016/j.bmcl.2006.12.099;
RA Di Fiore A., Scozzafava A., Winum J.-Y., Montero J.-L., Pedone C.,
RA Supuran C.T., De Simone G.;
RT "Carbonic anhydrase inhibitors: binding of an antiglaucoma glycosyl-
RT sulfanilamide derivative to human isoform II and its consequences for
RT the drug design of enzyme inhibitors incorporating sugar moieties.";
RL Bioorg. Med. Chem. Lett. 17:1726-1731(2007).
RN [86]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) IN COMPLEX WITH INHIBITOR
RP N-HYDROXYSULFAMIDE.
RX PubMed=17346964; DOI=10.1016/j.bmcl.2007.02.068;
RA Temperini C., Winum J.Y., Montero J.L., Scozzafava A., Supuran C.T.;
RT "Carbonic anhydrase inhibitors: the X-ray crystal structure of the
RT adduct of N-hydroxysulfamide with isozyme II explains why this new
RT zinc binding function is effective in the design of potent
RT inhibitors.";
RL Bioorg. Med. Chem. Lett. 17:2795-2801(2007).
RN [87]
RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) IN COMPLEX WITH INHIBITORS, AND
RP ENZYME REGULATION.
RX PubMed=17540563; DOI=10.1016/j.bmcl.2007.05.045;
RA Alterio V., De Simone G., Monti S.M., Scozzafava A., Supuran C.T.;
RT "Carbonic anhydrase inhibitors: inhibition of human, bacterial, and
RT archaeal isozymes with benzene-1,3-disulfonamides -- solution and
RT crystallographic studies.";
RL Bioorg. Med. Chem. Lett. 17:4201-4207(2007).
RN [88]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) IN COMPLEX WITH INHIBITORS, AND
RP ENZYME REGULATION.
RX PubMed=17588751; DOI=10.1016/j.bmcl.2007.06.044;
RA Temperini C., Innocenti A., Mastrolorenzo A., Scozzafava A.,
RA Supuran C.T.;
RT "Carbonic anhydrase inhibitors. Interaction of the antiepileptic drug
RT sulthiame with twelve mammalian isoforms: kinetic and X-ray
RT crystallographic studies.";
RL Bioorg. Med. Chem. Lett. 17:4866-4872(2007).
RN [89]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) IN COMPLEX WITH
RP 4-METHYLIMIDAZOLE, AND MUTAGENESIS OF TRP-5 AND HIS-64.
RX PubMed=17071654; DOI=10.1529/biophysj.106.093203;
RA Bhatt D., Fisher S.Z., Tu C., McKenna R., Silverman D.N.;
RT "Location of binding sites in small molecule rescue of human carbonic
RT anhydrase II.";
RL Biophys. J. 92:562-570(2007).
RN [90]
RP X-RAY CRYSTALLOGRAPHY (1.01 ANGSTROMS) IN COMPLEX WITH INHIBITORS.
RX PubMed=17407288; DOI=10.1021/ja068359w;
RA Srivastava D.K., Jude K.M., Banerjee A.L., Haldar M., Manokaran S.,
RA Kooren J., Mallik S., Christianson D.W.;
RT "Structural analysis of charge discrimination in the binding of
RT inhibitors to human carbonic anhydrases I and II.";
RL J. Am. Chem. Soc. 129:5528-5537(2007).
RN [91]
RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) IN COMPLEX WITH INHIBITOR
RP THIOXOLONE, AND ENZYME REGULATION.
RX PubMed=18266323; DOI=10.1021/bi702385k;
RA Barrese A.A. III, Genis C., Fisher S.Z., Orwenyo J.N., Kumara M.T.,
RA Dutta S.K., Phillips E., Kiddle J.J., Tu C., Silverman D.N.,
RA Govindasamy L., Agbandje-McKenna M., McKenna R., Tripp B.C.;
RT "Inhibition of carbonic anhydrase II by thioxolone: a mechanistic and
RT structural study.";
RL Biochemistry 47:3174-3184(2008).
RN [92]
RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF MUTANTS, MUTAGENESIS OF
RP ASN-62, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=18942852; DOI=10.1021/bi801473w;
RA Zheng J., Avvaru B.S., Tu C., McKenna R., Silverman D.N.;
RT "Role of hydrophilic residues in proton transfer during catalysis by
RT human carbonic anhydrase II.";
RL Biochemistry 47:12028-12036(2008).
RN [93]
RP X-RAY CRYSTALLOGRAPHY (1.89 ANGSTROMS) IN COMPLEX WITH INHIBITORS, AND
RP ENZYME REGULATION.
RX PubMed=18024029; DOI=10.1016/j.bmcl.2007.10.110;
RA Guezel O., Temperini C., Innocenti A., Scozzafava A., Salman A.,
RA Supuran C.T.;
RT "Carbonic anhydrase inhibitors. Interaction of 2-(hydrazinocarbonyl)-
RT 3-phenyl-1H-indole-5-sulfonamide with 12 mammalian isoforms: kinetic
RT and X-ray crystallographic studies.";
RL Bioorg. Med. Chem. Lett. 18:152-158(2008).
RN [94]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) IN COMPLEX WITH INHIBITORS, AND
RP ENZYME REGULATION.
RX PubMed=18162396; DOI=10.1016/j.bmcl.2007.12.022;
RA Temperini C., Cecchi A., Boyle N.A., Scozzafava A., Cabeza J.E.,
RA Wentworth P. Jr., Blackburn G.M., Supuran C.T.;
RT "Carbonic anhydrase inhibitors. Interaction of 2-N,N-dimethylamino-
RT 1,3,4-thiadiazole-5-methanesulfonamide with 12 mammalian isoforms:
RT kinetic and X-ray crystallographic studies.";
RL Bioorg. Med. Chem. Lett. 18:999-1005(2008).
RN [95]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) IN COMPLEX WITH INHIBITORS, AND
RP ENZYME REGULATION.
RX PubMed=18374572; DOI=10.1016/j.bmcl.2008.03.051;
RA Temperini C., Cecchi A., Scozzafava A., Supuran C.T.;
RT "Carbonic anhydrase inhibitors. Interaction of indapamide and related
RT diuretics with 12 mammalian isozymes and X-ray crystallographic
RT studies for the indapamide-isozyme II adduct.";
RL Bioorg. Med. Chem. Lett. 18:2567-2573(2008).
RN [96]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) IN COMPLEX WITH INHIBITORS.
RX PubMed=18359629; DOI=10.1016/j.bmcl.2008.03.023;
RA Di Fiore A., Pedone C., Antel J., Waldeck H., Witte A., Wurl M.,
RA Scozzafava A., Supuran C.T., De Simone G.;
RT "Carbonic anhydrase inhibitors: the X-ray crystal structure of
RT ethoxzolamide complexed to human isoform II reveals the importance of
RT thr200 and gln92 for obtaining tight-binding inhibitors.";
RL Bioorg. Med. Chem. Lett. 18:2669-2674(2008).
RN [97]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) IN COMPLEX WITH INHIBITORS, AND
RP ENZYME REGULATION.
RX PubMed=18640037; DOI=10.1016/j.bmcl.2008.06.105;
RA Temperini C., Innocenti A., Scozzafava A., Supuran C.T.;
RT "Carbonic anhydrase inhibitors. Interaction of the antitumor sulfamate
RT EMD 486019 with twelve mammalian carbonic anhydrase isoforms: Kinetic
RT and X-ray crystallographic studies.";
RL Bioorg. Med. Chem. Lett. 18:4282-4286(2008).
RN [98]
RP X-RAY CRYSTALLOGRAPHY (1.40 ANGSTROMS) IN COMPLEX WITH INHIBITORS
RP INDANESULFONAMIDES.
RX PubMed=18161740; DOI=10.1002/cmdc.200700274;
RA D'Ambrosio K., Masereel B., Thiry A., Scozzafava A., Supuran C.T.,
RA De Simone G.;
RT "Carbonic anhydrase inhibitors: binding of indanesulfonamides to the
RT human isoform II.";
RL ChemMedChem 3:473-477(2008).
RN [99]
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) IN COMPLEX WITH
RP (129)XE-CRYPTOPHANE BIOSENSOR.
RX PubMed=18461940; DOI=10.1021/ja802214x;
RA Aaron J.A., Chambers J.M., Jude K.M., Di Costanzo L., Dmochowski I.J.,
RA Christianson D.W.;
RT "Structure of a (129)Xe-cryptophane biosensor complexed with human
RT carbonic anhydrase II.";
RL J. Am. Chem. Soc. 130:6942-6943(2008).
RN [100]
RP X-RAY CRYSTALLOGRAPHY (1.10 ANGSTROMS) IN COMPLEX WITH CO2.
RX PubMed=18768466; DOI=10.1074/jbc.M805353200;
RA Domsic J.F., Avvaru B.S., Kim C.U., Gruner S.M., Agbandje-McKenna M.,
RA Silverman D.N., McKenna R.;
RT "Entrapment of carbon dioxide in the active site of carbonic anhydrase
RT II.";
RL J. Biol. Chem. 283:30766-30771(2008).
RN [101]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) IN COMPLEX WITH INHIBITORS.
RX PubMed=18260615; DOI=10.1021/jm701319c;
RA Leese M.P., Jourdan F.L., Gaukroger K., Mahon M.F., Newman S.P.,
RA Foster P.A., Stengel C., Regis-Lydi S., Ferrandis E., Di Fiore A.,
RA De Simone G., Supuran C.T., Purohit A., Reed M.J., Potter B.V.;
RT "Structure-activity relationships of C-17 cyano-substituted
RT estratrienes as anticancer agents.";
RL J. Med. Chem. 51:1295-1308(2008).
RN [102]
RP X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) IN COMPLEX WITH INHIBITORS, AND
RP ENZYME REGULATION.
RX PubMed=18481843; DOI=10.1021/jm800121c;
RA D'Ambrosio K., Vitale R.-M., Dogne J.-M., Masereel B., Innocenti A.,
RA Scozzafava A., De Simone G., Supuran C.T.;
RT "Carbonic anhydrase inhibitors: bioreductive nitro-containing
RT sulfonamides with selectivity for targeting the tumor associated
RT isoforms IX and XII.";
RL J. Med. Chem. 51:3230-3237(2008).
RN [103]
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) IN COMPLEX WITH INHIBITORS.
RX PubMed=18723489; DOI=10.1158/1535-7163.MCT-08-0195;
RA Woo L.W.L., Fischer D.S., Sharland C.M., Trusselle M., Foster P.A.,
RA Chander S.K., Di Fiore A., Supuran C.T., De Simone G., Purohit A.,
RA Reed M.J., Potter B.V.L.;
RT "Anticancer steroid sulfatase inhibitors: synthesis of a potent
RT fluorinated second-generation agent, in vitro and in vivo activities,
RT molecular modeling, and protein crystallography.";
RL Mol. Cancer Ther. 7:2435-2444(2008).
RN [104]
RP X-RAY CRYSTALLOGRAPHY (1.48 ANGSTROMS) IN COMPLEX WITH INHIBITORS,
RP ENZYME REGULATION, AND MUTAGENESIS OF ALA-65 AND ASN-67.
RX PubMed=19170619; DOI=10.1021/bi802035f;
RA Genis C., Sippel K.H., Case N., Cao W., Avvaru B.S., Tartaglia L.J.,
RA Govindasamy L., Tu C., Agbandje-McKenna M., Silverman D.N.,
RA Rosser C.J., McKenna R.;
RT "Design of a carbonic anhydrase IX active-site mimic to screen
RT inhibitors for possible anticancer properties.";
RL Biochemistry 48:1322-1331(2009).
RN [105]
RP X-RAY CRYSTALLOGRAPHY (1.26 ANGSTROMS) FREE AND IN COMPLEX WITH ZINC
RP ION, AND COFACTOR.
RX PubMed=19583303; DOI=10.1021/bi9007512;
RA Avvaru B.S., Busby S.A., Chalmers M.J., Griffin P.R.,
RA Venkatakrishnan B., Agbandje-McKenna M., Silverman D.N., McKenna R.;
RT "Apo-human carbonic anhydrase II revisited: implications of the loss
RT of a metal in protein structure, stability, and solvent network.";
RL Biochemistry 48:7365-7372(2009).
RN [106]
RP X-RAY CRYSTALLOGRAPHY (1.81 ANGSTROMS) OF 1-260 IN COMPLEX WITH
RP INHIBITOR THIABENDAZOLE-5-SULFONAMIDE, AND ENZYME REGULATION.
RX PubMed=19186056; DOI=10.1016/j.bmcl.2009.01.038;
RA Crocetti L., Maresca A., Temperini C., Hall R.A., Scozzafava A.,
RA Muehlschlegel F.A., Supuran C.T.;
RT "A thiabendazole sulfonamide shows potent inhibitory activity against
RT mammalian and nematode alpha-carbonic anhydrases.";
RL Bioorg. Med. Chem. Lett. 19:1371-1375(2009).
RN [107]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 1-260 IN COMPLEX WITH
RP COUMARIN INHIBITORS, AND ENZYME REGULATION.
RX PubMed=19206230; DOI=10.1021/ja809683v;
RA Maresca A., Temperini C., Vu H., Pham N.B., Poulsen S.-A.,
RA Scozzafava A., Quinn R.J., Supuran C.T.;
RT "Non-zinc mediated inhibition of carbonic anhydrases: coumarins are a
RT new class of suicide inhibitors.";
RL J. Am. Chem. Soc. 131:3057-3062(2009).
RN [108]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) IN COMPLEX WITH INHIBITORS.
RX PubMed=19115843; DOI=10.1021/jm801386n;
RA Temperini C., Cecchi A., Scozzafava A., Supuran C.T.;
RT "Carbonic anhydrase inhibitors. Comparison of chlorthalidone and
RT indapamide X-ray crystal structures in adducts with isozyme II: when
RT three water molecules and the keto-enol tautomerism make the
RT difference.";
RL J. Med. Chem. 52:322-328(2009).
RN [109]
RP X-RAY CRYSTALLOGRAPHY (1.41 ANGSTROMS) IN COMPLEX WITH INHIBITORS.
RX PubMed=19731956; DOI=10.1021/jm900641r;
RA Vitale R.M., Alterio V., Innocenti A., Winum J.-Y., Monti S.M.,
RA De Simone G., Supuran C.T.;
RT "Carbonic anhydrase inhibitors. Comparison of aliphatic sulfamate/bis-
RT sulfamate adducts with isozymes II and IX as a platform for designing
RT tight-binding, more isoform-selective inhibitors.";
RL J. Med. Chem. 52:5990-5998(2009).
RN [110]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 1-260 IN COMPLEX WITH
RP INHIBITORS.
RX PubMed=19827837; DOI=10.1021/jm900914e;
RA Lopez M., Paul B., Hofmann A., Morizzi J., Wu Q.K., Charman S.A.,
RA Innocenti A., Vullo D., Supuran C.T., Poulsen S.-A.;
RT "S-glycosyl primary sulfonamides--a new structural class for selective
RT inhibition of cancer-associated carbonic anhydrases.";
RL J. Med. Chem. 52:6421-6432(2009).
RN [111]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 1-260 IN COMPLEX WITH
RP INHIBITORS, AND ENZYME REGULATION.
RX PubMed=19778001; DOI=10.1021/jp906593c;
RA Ciani L., Cecchi A., Temperini C., Supuran C.T., Ristori S.;
RT "Dissecting the inhibition mechanism of cytosolic versus transmembrane
RT carbonic anhydrases by ESR.";
RL J. Phys. Chem. B 113:13998-14005(2009).
RN [112]
RP X-RAY CRYSTALLOGRAPHY (1.56 ANGSTROMS) IN COMPLEX WITH SUBSTRATES, AND
RP ENZYME REGULATION.
RX PubMed=19520834; DOI=10.1073/pnas.0904184106;
RA Sjoeblom B., Polentarutti M., Djinovic-Carugo K.;
RT "Structural study of X-ray induced activation of carbonic anhydrase.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:10609-10613(2009).
RN [113]
RP VARIANT JOGJAKARTA GLU-18.
RX PubMed=6817747; DOI=10.1007/BF00484072;
RA Jones G.L., Sofro A.S.M., Shaw D.C.;
RT "Chemical and enzymological characterization of an Indonesian variant
RT of human erythrocyte carbonic anhydrase II, CAII Jogjakarta (17 Lys
RT leads to Glu).";
RL Biochem. Genet. 20:979-1000(1982).
RN [114]
RP VARIANT MELBOURNE HIS-236.
RX PubMed=6407977; DOI=10.1007/BF00274768;
RA Jones G.L., Shaw D.C.;
RT "A chemical and enzymological comparison of the common major human
RT erythrocyte carbonic anhydrase II, its minor component, and a new
RT genetic variant, CA II Melbourne (237 Pro leads to His).";
RL Hum. Genet. 63:392-399(1983).
RN [115]
RP VARIANT OPTB3 TYR-107.
RX PubMed=1928091;
RA Venta P.J., Welty R.J., Johnson T.M., Sly W.S., Tashian R.E.;
RT "Carbonic anhydrase II deficiency syndrome in a Belgian family is
RT caused by a point mutation at an invariant histidine residue (107
RT His-->Tyr): complete structure of the normal human CA II gene.";
RL Am. J. Hum. Genet. 49:1082-1090(1991).
RN [116]
RP VARIANT OPTB3 TYR-107.
RX PubMed=1542674; DOI=10.1073/pnas.89.5.1804;
RA Roth D.E., Venta P.J., Tashian R.E., Sly W.S.;
RT "Molecular basis of human carbonic anhydrase II deficiency.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:1804-1808(1992).
RN [117]
RP VARIANT OPTB3 TYR-107.
RX PubMed=8834238; DOI=10.1007/s004390050068;
RA Soda H., Yukizane S., Yoshida I., Koga Y., Aramaki S., Kato H.;
RT "A point mutation in exon 3 (His 107-->Tyr) in two unrelated Japanese
RT patients with carbonic anhydrase II deficiency with central nervous
RT system involvement.";
RL Hum. Genet. 97:435-437(1996).
RN [118]
RP VARIANT OPTB3 PRO-92.
RX PubMed=9143915;
RX DOI=10.1002/(SICI)1098-1004(1997)9:5<383::AID-HUMU1>3.3.CO;2-K;
RA Hu P.Y., Lim E.J., Ciccolella J., Strisciuglio P., Sly W.S.;
RT "Seven novel mutations in carbonic anhydrase II deficiency syndrome
RT identified by SSCP and direct sequencing analysis.";
RL Hum. Mutat. 9:383-387(1997).
RN [119]
RP VARIANTS OPTB3 PRO-92; TYR-94; TYR-107 AND ARG-144, AND
RP CHARACTERIZATION OF VARIANTS TYR-94 AND ARG-144.
RX PubMed=15300855; DOI=10.1002/humu.9266;
RA Shah G.N., Bonapace G., Hu P.Y., Strisciuglio P., Sly W.S.;
RT "Carbonic anhydrase II deficiency syndrome (osteopetrosis with renal
RT tubular acidosis and brain calcification): novel mutations in CA2
RT identified by direct sequencing expand the opportunity for genotype-
RT phenotype correlation.";
RL Hum. Mutat. 24:272-272(2004).
CC -!- FUNCTION: Essential for bone resorption and osteoclast
CC differentiation (By similarity). Reversible hydration of carbon
CC dioxide. Can hydrate cyanamide to urea. Involved in the regulation
CC of fluid secretion into the anterior chamber of the eye.
CC Contributes to intracellular pH regulation in the duodenal upper
CC villous epithelium during proton-coupled peptide absorption.
CC Stimulates the chloride-bicarbonate exchange activity of SLC26A6.
CC -!- CATALYTIC ACTIVITY: H(2)CO(3) = CO(2) + H(2)O.
CC -!- COFACTOR: Zinc. Can also use cobalt(II) with lower efficiency, but
CC not copper(II), nickel(II) and manganese(II).
CC -!- ENZYME REGULATION: Activated by X-ray, histamine, L-adrenaline, L-
CC and D-phenylalanine, L- and D-histidine, L-His-OMe and beta-Ala-
CC His (carnosine). Competitively inhibited by saccharin, thioxolone,
CC coumarins, 667-coumate, celecoxib (Celebrex), valdecoxib (Bextra),
CC SC-125, SC-560, diclofenac, acetate, azide, bromide, sulfonamide
CC derivatives such as acetazolamide (AZA), methazolamide (MZA),
CC ethoxzolamide (EZA), dichlorophenamide (DCP), brinzolamide,
CC dansylamide, thiabendazole-5-sulfonamide, trifluoromethane
CC sulfonamide and N-hydroxysulfamide, fructose-based sugar sulfamate
CC RWJ-37497, and Foscarnet (phosphonoformate trisodium salt).
CC Repressed strongly by hydrogen sulfide(HS) and weakly by nitrate
CC (NO(3)). Esterase activity weakly reduced by cyanamide. N-
CC hydroxyurea interfers with zinc binding and inhibit activity.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Absorption:
CC Abs(max)=550 nm;
CC Note=At pH 7.0. Shows a second maximum at 618 nm;
CC Kinetic parameters:
CC KM=10 mM for CO(2);
CC KM=82 mM for H(2)CO(3);
CC KM=3 mM for 4-nitrophenyl acetate;
CC pH dependence:
CC Optimum pH is 6-8;
CC -!- SUBUNIT: Interacts with SLC4A4. Interaction with SLC4A7 regulates
CC SLC4A7 transporter activity. Interacts with SLC26A6 isoform 4 (via
CC C-terminus cytoplasmic domain).
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cell membrane. Note=Colocalized
CC with SLC26A6 at the surface of the cell membrane in order to form
CC a bicarbonate transport metabolon. Displaced from the cytosolic
CC surface of the cell membrane by PKC in phorbol myristate acetate
CC (PMA)-induced cells.
CC -!- DISEASE: Osteopetrosis, autosomal recessive 3 (OPTB3)
CC [MIM:259730]: A rare genetic disease characterized by abnormally
CC dense bone, due to defective resorption of immature bone.
CC Osteopetrosis occurs in two forms: a severe autosomal recessive
CC form occurring in utero, infancy, or childhood, and a benign
CC autosomal dominant form occurring in adolescence or adulthood.
CC Recessive osteopetrosis commonly manifests in early infancy with
CC macrocephaly, feeding difficulties, evolving blindness and
CC deafness, bone marrow failure, severe anemia, and
CC hepatosplenomegaly. Deafness and blindness are generally thought
CC to represent effects of pressure on nerves. OPTB3 is associated
CC with renal tubular acidosis, cerebral calcification (marble brain
CC disease) and in some cases with mental retardation. Note=The
CC disease is caused by mutations affecting the gene represented in
CC this entry.
CC -!- MISCELLANEOUS: Target of drugs used in treatments against glaucoma
CC disorder and breast cancer.
CC -!- SIMILARITY: Belongs to the alpha-carbonic anhydrase family.
CC -!- WEB RESOURCE: Name=GeneReviews;
CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/CA2";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
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DR EMBL; M77181; AAA51909.1; -; Genomic_DNA.
DR EMBL; M77176; AAA51909.1; JOINED; Genomic_DNA.
DR EMBL; M77177; AAA51909.1; JOINED; Genomic_DNA.
DR EMBL; M77178; AAA51909.1; JOINED; Genomic_DNA.
DR EMBL; M77179; AAA51909.1; JOINED; Genomic_DNA.
DR EMBL; M77180; AAA51909.1; JOINED; Genomic_DNA.
DR EMBL; Y00339; CAA68426.1; -; mRNA.
DR EMBL; X03251; CAA27012.1; -; Genomic_DNA.
DR EMBL; J03037; AAA51908.1; -; mRNA.
DR EMBL; CR536526; CAG38763.1; -; mRNA.
DR EMBL; CR541875; CAG46673.1; -; mRNA.
DR EMBL; AK312978; BAG35815.1; -; mRNA.
DR EMBL; CH471068; EAW87136.1; -; Genomic_DNA.
DR EMBL; BC011949; AAH11949.1; -; mRNA.
DR EMBL; M36532; AAA51911.1; -; mRNA.
DR PIR; A27175; CRHU2.
DR RefSeq; NP_000058.1; NM_000067.2.
DR UniGene; Hs.155097; -.
DR PDB; 12CA; X-ray; 2.40 A; A=2-260.
DR PDB; 1A42; X-ray; 2.25 A; A=2-260.
DR PDB; 1AM6; X-ray; 2.00 A; A=2-260.
DR PDB; 1AVN; X-ray; 2.00 A; A=2-260.
DR PDB; 1BCD; X-ray; 1.90 A; A=2-260.
DR PDB; 1BIC; X-ray; 1.90 A; A=2-260.
DR PDB; 1BN1; X-ray; 2.10 A; A=2-260.
DR PDB; 1BN3; X-ray; 2.20 A; A=2-260.
DR PDB; 1BN4; X-ray; 2.10 A; A=2-260.
DR PDB; 1BNM; X-ray; 2.60 A; A=2-260.
DR PDB; 1BNN; X-ray; 2.30 A; A=2-260.
DR PDB; 1BNQ; X-ray; 2.40 A; A=2-260.
DR PDB; 1BNT; X-ray; 2.15 A; A=2-260.
DR PDB; 1BNU; X-ray; 2.15 A; A=2-260.
DR PDB; 1BNV; X-ray; 2.40 A; A=2-260.
DR PDB; 1BNW; X-ray; 2.25 A; A=2-260.
DR PDB; 1BV3; X-ray; 1.85 A; A=2-260.
DR PDB; 1CA2; X-ray; 2.00 A; A=2-260.
DR PDB; 1CA3; X-ray; 2.30 A; A=2-260.
DR PDB; 1CAH; X-ray; 1.88 A; A=2-260.
DR PDB; 1CAI; X-ray; 1.80 A; A=2-260.
DR PDB; 1CAJ; X-ray; 1.90 A; A=2-260.
DR PDB; 1CAK; X-ray; 1.90 A; A=2-260.
DR PDB; 1CAL; X-ray; 2.20 A; A=2-260.
DR PDB; 1CAM; X-ray; 1.70 A; A=2-260.
DR PDB; 1CAN; X-ray; 1.90 A; A=2-260.
DR PDB; 1CAO; X-ray; 1.90 A; A=2-260.
DR PDB; 1CAY; X-ray; 2.10 A; A=2-260.
DR PDB; 1CAZ; X-ray; 1.90 A; A=2-260.
DR PDB; 1CCS; X-ray; 2.35 A; A=2-260.
DR PDB; 1CCT; X-ray; 2.20 A; A=2-260.
DR PDB; 1CCU; X-ray; 2.25 A; A=2-260.
DR PDB; 1CIL; X-ray; 1.60 A; A=2-260.
DR PDB; 1CIM; X-ray; 2.10 A; A=2-260.
DR PDB; 1CIN; X-ray; 2.10 A; A=2-260.
DR PDB; 1CNB; X-ray; 2.35 A; A=2-260.
DR PDB; 1CNC; X-ray; 2.20 A; A=2-260.
DR PDB; 1CNG; X-ray; 1.90 A; A=2-260.
DR PDB; 1CNH; X-ray; 2.05 A; A=2-260.
DR PDB; 1CNI; X-ray; 1.80 A; A=2-260.
DR PDB; 1CNJ; X-ray; 1.80 A; A=2-260.
DR PDB; 1CNK; X-ray; 2.15 A; A=2-260.
DR PDB; 1CNW; X-ray; 2.00 A; A=2-260.
DR PDB; 1CNX; X-ray; 1.90 A; A=2-260.
DR PDB; 1CNY; X-ray; 2.30 A; A=2-260.
DR PDB; 1CRA; X-ray; 1.90 A; A=2-260.
DR PDB; 1CVA; X-ray; 2.25 A; A=2-260.
DR PDB; 1CVB; X-ray; 2.40 A; A=2-260.
DR PDB; 1CVC; X-ray; 2.30 A; A=2-260.
DR PDB; 1CVD; X-ray; 2.20 A; A=2-258.
DR PDB; 1CVE; X-ray; 2.25 A; A=2-260.
DR PDB; 1CVF; X-ray; 2.25 A; A=2-260.
DR PDB; 1CVH; X-ray; 2.30 A; A=2-259.
DR PDB; 1DCA; X-ray; 2.20 A; A=2-260.
DR PDB; 1DCB; X-ray; 2.10 A; A=2-260.
DR PDB; 1EOU; X-ray; 2.10 A; A=2-260.
DR PDB; 1F2W; X-ray; 1.90 A; A=2-260.
DR PDB; 1FQL; X-ray; 2.00 A; A=2-260.
DR PDB; 1FQM; X-ray; 2.00 A; A=2-260.
DR PDB; 1FQN; X-ray; 2.00 A; A=2-260.
DR PDB; 1FQR; X-ray; 2.00 A; A=2-260.
DR PDB; 1FR4; X-ray; 1.60 A; A=2-260.
DR PDB; 1FR7; X-ray; 1.50 A; A/B=2-260.
DR PDB; 1FSN; X-ray; 2.00 A; A/B=2-260.
DR PDB; 1FSQ; X-ray; 2.00 A; A/B=2-260.
DR PDB; 1FSR; X-ray; 2.00 A; A/B=2-260.
DR PDB; 1G0E; X-ray; 1.60 A; A=2-260.
DR PDB; 1G0F; X-ray; 1.60 A; A=2-260.
DR PDB; 1G1D; X-ray; 2.04 A; A=2-260.
DR PDB; 1G3Z; X-ray; 1.86 A; A=2-260.
DR PDB; 1G45; X-ray; 1.83 A; A=2-260.
DR PDB; 1G46; X-ray; 1.84 A; A=2-260.
DR PDB; 1G48; X-ray; 1.86 A; A=2-260.
DR PDB; 1G4J; X-ray; 1.84 A; A=2-260.
DR PDB; 1G4O; X-ray; 1.96 A; A=2-260.
DR PDB; 1G52; X-ray; 1.80 A; A=2-260.
DR PDB; 1G53; X-ray; 1.94 A; A=2-260.
DR PDB; 1G54; X-ray; 1.86 A; A=2-259.
DR PDB; 1H4N; X-ray; 2.00 A; A=2-260.
DR PDB; 1H9N; X-ray; 1.85 A; A=2-260.
DR PDB; 1H9Q; X-ray; 2.20 A; A=2-260.
DR PDB; 1HCA; X-ray; 2.30 A; A=2-260.
DR PDB; 1HEA; X-ray; 2.00 A; A=2-260.
DR PDB; 1HEB; X-ray; 2.00 A; A=2-260.
DR PDB; 1HEC; X-ray; 2.00 A; A=2-260.
DR PDB; 1HED; X-ray; 2.00 A; A=2-260.
DR PDB; 1HVA; X-ray; 2.30 A; A=2-260.
DR PDB; 1I8Z; X-ray; 1.93 A; A=2-260.
DR PDB; 1I90; X-ray; 2.00 A; A=2-260.
DR PDB; 1I91; X-ray; 2.00 A; A=2-260.
DR PDB; 1I9L; X-ray; 1.93 A; A=2-260.
DR PDB; 1I9M; X-ray; 1.84 A; A=2-260.
DR PDB; 1I9N; X-ray; 1.86 A; A=2-260.
DR PDB; 1I9O; X-ray; 1.86 A; A=2-260.
DR PDB; 1I9P; X-ray; 1.92 A; A=2-260.
DR PDB; 1I9Q; X-ray; 1.80 A; A=2-260.
DR PDB; 1IF4; X-ray; 1.93 A; A=2-260.
DR PDB; 1IF5; X-ray; 2.00 A; A=2-260.
DR PDB; 1IF6; X-ray; 2.09 A; A=2-260.
DR PDB; 1IF7; X-ray; 1.98 A; A=2-260.
DR PDB; 1IF8; X-ray; 1.94 A; A=2-260.
DR PDB; 1IF9; X-ray; 2.00 A; A=2-260.
DR PDB; 1KWQ; X-ray; 2.60 A; A=2-260.
DR PDB; 1KWR; X-ray; 2.25 A; A=2-260.
DR PDB; 1LG5; X-ray; 1.75 A; A=2-260.
DR PDB; 1LG6; X-ray; 2.20 A; A=2-260.
DR PDB; 1LGD; X-ray; 1.90 A; A=2-260.
DR PDB; 1LUG; X-ray; 0.95 A; A=2-260.
DR PDB; 1LZV; X-ray; 2.30 A; A=2-260.
DR PDB; 1MOO; X-ray; 1.05 A; A=2-260.
DR PDB; 1MUA; X-ray; 1.70 A; A=2-260.
DR PDB; 1OKL; X-ray; 2.10 A; A=2-260.
DR PDB; 1OKM; X-ray; 2.20 A; A=2-260.
DR PDB; 1OKN; X-ray; 2.40 A; A=2-260.
DR PDB; 1OQ5; X-ray; 1.50 A; A=2-260.
DR PDB; 1RAY; X-ray; 1.80 A; A=2-260.
DR PDB; 1RAZ; X-ray; 1.90 A; A=2-260.
DR PDB; 1RZA; X-ray; 1.90 A; A=2-260.
DR PDB; 1RZB; X-ray; 1.80 A; A=2-260.
DR PDB; 1RZC; X-ray; 1.90 A; A=2-260.
DR PDB; 1RZD; X-ray; 1.90 A; A=2-260.
DR PDB; 1RZE; X-ray; 1.90 A; A=2-260.
DR PDB; 1T9N; X-ray; 2.00 A; A=2-260.
DR PDB; 1TB0; X-ray; 2.00 A; X=2-260.
DR PDB; 1TBT; X-ray; 2.00 A; X=2-260.
DR PDB; 1TE3; X-ray; 2.00 A; X=2-260.
DR PDB; 1TEQ; X-ray; 2.00 A; X=2-260.
DR PDB; 1TEU; X-ray; 2.00 A; X=2-260.
DR PDB; 1TG3; X-ray; 1.80 A; A=2-260.
DR PDB; 1TG9; X-ray; 1.90 A; A=2-260.
DR PDB; 1TH9; X-ray; 1.63 A; A=2-260.
DR PDB; 1THK; X-ray; 1.80 A; A=2-260.
DR PDB; 1TTM; X-ray; 1.95 A; A=2-260.
DR PDB; 1UGA; X-ray; 2.00 A; A=2-260.
DR PDB; 1UGB; X-ray; 2.00 A; A=2-260.
DR PDB; 1UGC; X-ray; 2.00 A; A=2-260.
DR PDB; 1UGD; X-ray; 2.00 A; A=2-260.
DR PDB; 1UGE; X-ray; 1.90 A; A=2-260.
DR PDB; 1UGF; X-ray; 2.00 A; A=2-260.
DR PDB; 1UGG; X-ray; 2.20 A; A=2-260.
DR PDB; 1XEG; X-ray; 1.81 A; A=2-260.
DR PDB; 1XEV; X-ray; 2.20 A; A/B/C/D=2-260.
DR PDB; 1XPZ; X-ray; 2.02 A; A=2-260.
DR PDB; 1XQ0; X-ray; 1.76 A; A=2-260.
DR PDB; 1YDA; X-ray; 2.10 A; A=2-260.
DR PDB; 1YDB; X-ray; 1.90 A; A=2-260.
DR PDB; 1YDC; X-ray; 1.95 A; A=2-260.
DR PDB; 1YDD; X-ray; 2.10 A; A=2-260.
DR PDB; 1YO0; X-ray; 1.80 A; A=2-260.
DR PDB; 1YO1; X-ray; 1.70 A; A=2-260.
DR PDB; 1YO2; X-ray; 1.80 A; A=2-260.
DR PDB; 1Z9Y; X-ray; 1.66 A; A=2-260.
DR PDB; 1ZE8; X-ray; 2.00 A; A=2-260.
DR PDB; 1ZFK; X-ray; 1.56 A; A=2-260.
DR PDB; 1ZFQ; X-ray; 1.55 A; A=2-260.
DR PDB; 1ZGE; X-ray; 1.65 A; A=2-260.
DR PDB; 1ZGF; X-ray; 1.75 A; A=2-260.
DR PDB; 1ZH9; X-ray; 1.70 A; A=2-260.
DR PDB; 1ZSA; X-ray; 2.50 A; A=2-260.
DR PDB; 1ZSB; X-ray; 2.00 A; A=2-260.
DR PDB; 1ZSC; X-ray; 1.80 A; A=2-260.
DR PDB; 2ABE; X-ray; 2.00 A; A=2-260.
DR PDB; 2AW1; X-ray; 1.46 A; A=2-260.
DR PDB; 2AX2; X-ray; 1.50 A; A=2-260.
DR PDB; 2CA2; X-ray; 1.90 A; A=2-260.
DR PDB; 2CBA; X-ray; 1.54 A; A=2-260.
DR PDB; 2CBB; X-ray; 1.67 A; A=2-260.
DR PDB; 2CBC; X-ray; 1.88 A; A=2-260.
DR PDB; 2CBD; X-ray; 1.67 A; A=2-260.
DR PDB; 2CBE; X-ray; 1.82 A; A=2-260.
DR PDB; 2EU2; X-ray; 1.15 A; A=2-260.
DR PDB; 2EU3; X-ray; 1.60 A; A=2-260.
DR PDB; 2EZ7; X-ray; 2.00 A; A=2-260.
DR PDB; 2F14; X-ray; 1.71 A; A=2-260.
DR PDB; 2FMG; X-ray; 1.60 A; A=2-260.
DR PDB; 2FMZ; X-ray; 1.60 A; A=2-260.
DR PDB; 2FNK; X-ray; 1.80 A; A=2-260.
DR PDB; 2FNM; X-ray; 1.80 A; A=2-260.
DR PDB; 2FNN; X-ray; 1.80 A; A=2-260.
DR PDB; 2FOQ; X-ray; 1.25 A; A=2-260.
DR PDB; 2FOS; X-ray; 1.10 A; A=2-260.
DR PDB; 2FOU; X-ray; 0.99 A; A=2-260.
DR PDB; 2FOV; X-ray; 1.15 A; A=2-260.
DR PDB; 2GD8; X-ray; 1.46 A; A=2-260.
DR PDB; 2GEH; X-ray; 2.00 A; A=2-260.
DR PDB; 2H15; X-ray; 1.90 A; A=2-260.
DR PDB; 2H4N; X-ray; 1.90 A; A=2-260.
DR PDB; 2HD6; X-ray; 1.80 A; A=2-260.
DR PDB; 2HKK; X-ray; 1.90 A; A=2-260.
DR PDB; 2HL4; X-ray; 1.55 A; A=2-260.
DR PDB; 2HNC; X-ray; 1.55 A; A=2-260.
DR PDB; 2HOC; X-ray; 2.10 A; A=2-260.
DR PDB; 2ILI; X-ray; 1.05 A; A=2-260.
DR PDB; 2NNG; X-ray; 1.20 A; A=2-260.
DR PDB; 2NNO; X-ray; 1.01 A; A=2-260.
DR PDB; 2NNS; X-ray; 1.03 A; A=2-260.
DR PDB; 2NNV; X-ray; 1.10 A; A=2-260.
DR PDB; 2NWO; X-ray; 1.70 A; A=2-260.
DR PDB; 2NWP; X-ray; 1.80 A; A=2-260.
DR PDB; 2NWY; X-ray; 1.65 A; A=2-260.
DR PDB; 2NWZ; X-ray; 1.80 A; A=2-260.
DR PDB; 2NXR; X-ray; 1.70 A; A=2-260.
DR PDB; 2NXS; X-ray; 1.80 A; A=2-260.
DR PDB; 2NXT; X-ray; 1.15 A; A=2-260.
DR PDB; 2O4Z; X-ray; 2.10 A; A=2-260.
DR PDB; 2OSF; X-ray; 1.60 A; A=2-260.
DR PDB; 2OSM; X-ray; 1.60 A; A=2-260.
DR PDB; 2POU; X-ray; 1.60 A; A=2-260.
DR PDB; 2POV; X-ray; 1.60 A; A=2-260.
DR PDB; 2POW; X-ray; 1.75 A; A=2-260.
DR PDB; 2Q1B; X-ray; 1.70 A; A=2-260.
DR PDB; 2Q1Q; X-ray; 1.90 A; A=2-260.
DR PDB; 2Q38; X-ray; 1.95 A; A=2-260.
DR PDB; 2QO8; X-ray; 1.40 A; A=2-260.
DR PDB; 2QOA; X-ray; 1.60 A; A=2-260.
DR PDB; 2QP6; X-ray; 1.45 A; A=2-260.
DR PDB; 2VVA; X-ray; 1.56 A; X=2-260.
DR PDB; 2VVB; X-ray; 1.66 A; X=2-260.
DR PDB; 2WD2; X-ray; 1.49 A; A=2-260.
DR PDB; 2WD3; X-ray; 1.80 A; A=2-260.
DR PDB; 2WEG; X-ray; 1.10 A; A=2-260.
DR PDB; 2WEH; X-ray; 2.09 A; A=2-260.
DR PDB; 2WEJ; X-ray; 1.45 A; A=2-260.
DR PDB; 2WEO; X-ray; 1.40 A; A=2-260.
DR PDB; 2X7S; X-ray; 1.64 A; A=2-260.
DR PDB; 2X7T; X-ray; 1.89 A; A=2-260.
DR PDB; 2X7U; X-ray; 2.12 A; A=2-260.
DR PDB; 3B4F; X-ray; 1.89 A; A=2-260.
DR PDB; 3BET; X-ray; 1.85 A; A=2-260.
DR PDB; 3BL0; X-ray; 1.90 A; A=2-260.
DR PDB; 3BL1; X-ray; 2.10 A; A=2-260.
DR PDB; 3C7P; X-ray; 1.70 A; A=2-260.
DR PDB; 3CA2; X-ray; 2.00 A; A=2-260.
DR PDB; 3CAJ; X-ray; 1.80 A; A=2-260.
DR PDB; 3CYU; X-ray; 1.70 A; A=2-260.
DR PDB; 3D8W; X-ray; 1.70 A; A=2-260.
DR PDB; 3D92; X-ray; 1.10 A; A=2-260.
DR PDB; 3D93; X-ray; 1.10 A; A=2-260.
DR PDB; 3D9Z; X-ray; 1.65 A; A=2-260.
DR PDB; 3DAZ; X-ray; 1.60 A; A=2-260.
DR PDB; 3DBU; X-ray; 1.70 A; A=2-260.
DR PDB; 3DC3; X-ray; 1.70 A; A=2-260.
DR PDB; 3DC9; X-ray; 1.60 A; A=2-260.
DR PDB; 3DCC; X-ray; 1.60 A; A=2-260.
DR PDB; 3DCS; X-ray; 1.80 A; A=2-260.
DR PDB; 3DCW; X-ray; 1.50 A; A=2-260.
DR PDB; 3DD0; X-ray; 1.48 A; A=2-260.
DR PDB; 3DD8; X-ray; 1.90 A; A=2-260.
DR PDB; 3DV7; X-ray; 1.70 A; A=2-260.
DR PDB; 3DVB; X-ray; 1.70 A; A=2-260.
DR PDB; 3DVC; X-ray; 1.60 A; A=2-260.
DR PDB; 3DVD; X-ray; 1.60 A; A=2-260.
DR PDB; 3EFI; X-ray; 1.75 A; A=2-260.
DR PDB; 3EFT; X-ray; 1.85 A; A=1-260.
DR PDB; 3F4X; X-ray; 1.90 A; A=2-260.
DR PDB; 3F8E; X-ray; 2.00 A; A=1-260.
DR PDB; 3FFP; X-ray; 1.81 A; X=1-260.
DR PDB; 3GZ0; X-ray; 1.26 A; A=2-260.
DR PDB; 3HFP; X-ray; 2.10 A; A=1-260.
DR PDB; 3HKN; X-ray; 1.80 A; A=1-260.
DR PDB; 3HKQ; X-ray; 1.70 A; A=1-260.
DR PDB; 3HKT; X-ray; 2.36 A; A=1-260.
DR PDB; 3HKU; X-ray; 1.80 A; A=1-260.
DR PDB; 3HLJ; X-ray; 1.44 A; A=1-260.
DR PDB; 3HS4; X-ray; 1.10 A; A=1-260.
DR PDB; 3IBI; X-ray; 1.93 A; A=2-260.
DR PDB; 3IBL; X-ray; 1.55 A; A=2-260.
DR PDB; 3IBN; X-ray; 2.20 A; A=2-260.
DR PDB; 3IBU; X-ray; 1.41 A; A=2-260.
DR PDB; 3IEO; X-ray; 2.00 A; A=1-260.
DR PDB; 3IGP; X-ray; 1.65 A; A=1-260.
DR PDB; 3K2F; X-ray; 1.98 A; A=1-260.
DR PDB; 3K34; X-ray; 0.90 A; A=1-260.
DR PDB; 3K7K; X-ray; 1.90 A; A=1-260.
DR PDB; 3KIG; X-ray; 1.39 A; A=1-260.
DR PDB; 3KKX; Neutron; 2.00 A; A=1-260.
DR PDB; 3KNE; X-ray; 1.35 A; A=1-260.
DR PDB; 3KOI; X-ray; 1.64 A; A=1-260.
DR PDB; 3KOK; X-ray; 1.50 A; A=1-260.
DR PDB; 3KON; X-ray; 1.50 A; A=1-260.
DR PDB; 3KS3; X-ray; 0.90 A; A=1-260.
DR PDB; 3KWA; X-ray; 2.00 A; A=1-260.
DR PDB; 3L14; X-ray; 1.22 A; A=1-260.
DR PDB; 3M04; X-ray; 1.40 A; A=1-260.
DR PDB; 3M14; X-ray; 1.38 A; A=1-260.
DR PDB; 3M1J; X-ray; 1.80 A; A=1-260.
DR PDB; 3M1K; X-ray; 1.35 A; A=1-260.
DR PDB; 3M1Q; X-ray; 1.69 A; A=1-260.
DR PDB; 3M1W; X-ray; 1.38 A; A=1-260.
DR PDB; 3M2N; X-ray; 1.65 A; A=1-260.
DR PDB; 3M2X; X-ray; 1.87 A; A=1-260.
DR PDB; 3M2Y; X-ray; 1.17 A; A=1-260.
DR PDB; 3M2Z; X-ray; 1.70 A; A=1-260.
DR PDB; 3M3X; X-ray; 1.68 A; A=1-260.
DR PDB; 3M40; X-ray; 1.60 A; A=1-260.
DR PDB; 3M5E; X-ray; 1.70 A; A=1-260.
DR PDB; 3M5S; X-ray; 1.40 A; A=1-260.
DR PDB; 3M5T; X-ray; 1.95 A; A=1-260.
DR PDB; 3M67; X-ray; 1.80 A; A=1-260.
DR PDB; 3M96; X-ray; 1.40 A; A=1-260.
DR PDB; 3M98; X-ray; 1.50 A; A=1-260.
DR PDB; 3MHC; X-ray; 1.70 A; A=1-260.
DR PDB; 3MHI; X-ray; 1.70 A; A=1-260.
DR PDB; 3MHL; X-ray; 1.90 A; A=1-260.
DR PDB; 3MHM; X-ray; 1.50 A; A=1-260.
DR PDB; 3MHO; X-ray; 1.15 A; A=1-260.
DR PDB; 3ML2; X-ray; 1.80 A; A=1-260.
DR PDB; 3MMF; X-ray; 1.50 A; A=1-260.
DR PDB; 3MNA; X-ray; 1.50 A; A=1-260.
DR PDB; 3MNH; X-ray; 1.65 A; A=1-260.
DR PDB; 3MNI; X-ray; 1.75 A; A=1-260.
DR PDB; 3MNJ; X-ray; 1.75 A; A=1-260.
DR PDB; 3MNK; X-ray; 1.75 A; A=1-260.
DR PDB; 3MNU; X-ray; 1.80 A; A=2-260.
DR PDB; 3MWO; X-ray; 1.40 A; A/B=1-260.
DR PDB; 3MYQ; X-ray; 1.35 A; A=1-260.
DR PDB; 3MZC; X-ray; 1.50 A; A=1-260.
DR PDB; 3N0N; X-ray; 1.50 A; A=1-260.
DR PDB; 3N2P; X-ray; 1.65 A; A=1-260.
DR PDB; 3N3J; X-ray; 1.50 A; A=1-260.
DR PDB; 3N4B; X-ray; 1.60 A; A=1-260.
DR PDB; 3NB5; X-ray; 1.80 A; A=1-260.
DR PDB; 3NI5; X-ray; 2.10 A; A=1-260.
DR PDB; 3NJ9; X-ray; 2.00 A; A=1-260.
DR PDB; 3OIK; X-ray; 1.50 A; A=1-260.
DR PDB; 3OIL; X-ray; 1.50 A; A=1-260.
DR PDB; 3OIM; X-ray; 1.45 A; A=1-260.
DR PDB; 3OKU; X-ray; 1.45 A; A=1-260.
DR PDB; 3OKV; X-ray; 1.45 A; A=1-260.
DR PDB; 3OY0; X-ray; 1.60 A; A=1-260.
DR PDB; 3OYQ; X-ray; 1.47 A; A=1-260.
DR PDB; 3OYS; X-ray; 1.54 A; A=1-260.
DR PDB; 3P3H; X-ray; 1.50 A; A=1-260.
DR PDB; 3P3J; X-ray; 1.60 A; A=1-260.
DR PDB; 3P44; X-ray; 2.20 A; A=1-260.
DR PDB; 3P4V; X-ray; 2.00 A; A=1-260.
DR PDB; 3P55; X-ray; 2.00 A; A=1-260.
DR PDB; 3P58; X-ray; 1.49 A; A=1-260.
DR PDB; 3P5A; X-ray; 1.49 A; A=1-260.
DR PDB; 3P5L; X-ray; 1.50 A; A=1-260.
DR PDB; 3PJJ; X-ray; 1.80 A; A=2-260.
DR PDB; 3PO6; X-ray; 1.47 A; A=2-260.
DR PDB; 3PYK; X-ray; 1.30 A; A=3-260.
DR PDB; 3QYK; X-ray; 1.47 A; A=1-260.
DR PDB; 3R16; X-ray; 1.60 A; A=4-260.
DR PDB; 3R17; X-ray; 1.70 A; B=4-260.
DR PDB; 3RG3; X-ray; 1.90 A; A=1-260.
DR PDB; 3RG4; X-ray; 1.50 A; A=1-260.
DR PDB; 3RGE; X-ray; 2.10 A; A=1-260.
DR PDB; 3RJ7; X-ray; 1.20 A; A=3-260.
DR PDB; 3RLD; X-ray; 1.50 A; A=1-260.
DR PDB; 3RYJ; X-ray; 1.39 A; B=2-260.
DR PDB; 3RYV; X-ray; 1.20 A; B=2-260.
DR PDB; 3RYX; X-ray; 1.60 A; B=2-260.
DR PDB; 3RYY; X-ray; 1.16 A; A=2-260.
DR PDB; 3RYZ; X-ray; 1.37 A; A=2-260.
DR PDB; 3RZ0; X-ray; 1.80 A; B=2-260.
DR PDB; 3RZ1; X-ray; 1.51 A; B=2-260.
DR PDB; 3RZ5; X-ray; 1.65 A; A=2-260.
DR PDB; 3RZ7; X-ray; 1.80 A; A=2-260.
DR PDB; 3RZ8; X-ray; 1.70 A; A=2-260.
DR PDB; 3S71; X-ray; 1.25 A; B=3-260.
DR PDB; 3S72; X-ray; 1.60 A; B=3-260.
DR PDB; 3S73; X-ray; 1.75 A; B=3-260.
DR PDB; 3S74; X-ray; 1.40 A; B=3-260.
DR PDB; 3S75; X-ray; 1.50 A; B=3-260.
DR PDB; 3S76; X-ray; 1.60 A; A=3-260.
DR PDB; 3S77; X-ray; 1.86 A; B=3-260.
DR PDB; 3S78; X-ray; 1.98 A; B=3-260.
DR PDB; 3S8X; X-ray; 1.30 A; A=1-260.
DR PDB; 3S9T; X-ray; 1.30 A; A=1-260.
DR PDB; 3SAP; X-ray; 1.75 A; A=1-260.
DR PDB; 3SAX; X-ray; 1.10 A; A=1-260.
DR PDB; 3SBH; X-ray; 1.65 A; A=1-260.
DR PDB; 3SBI; X-ray; 1.40 A; A=1-260.
DR PDB; 3T5U; X-ray; 1.75 A; A=2-260.
DR PDB; 3T5Z; X-ray; 1.65 A; A=2-260.
DR PDB; 3T82; X-ray; 2.00 A; A=1-260.
DR PDB; 3T83; X-ray; 1.80 A; A=1-260.
DR PDB; 3T84; X-ray; 2.00 A; A=1-260.
DR PDB; 3T85; X-ray; 2.40 A; A=1-260.
DR PDB; 3TMJ; Other; 2.00 A; A=3-260.
DR PDB; 3TVN; X-ray; 1.50 A; X=3-260.
DR PDB; 3TVO; X-ray; 1.60 A; X=3-260.
DR PDB; 3U3A; X-ray; 1.55 A; X=1-260.
DR PDB; 3U45; X-ray; 1.70 A; X=1-260.
DR PDB; 3U47; X-ray; 1.60 A; A=1-260.
DR PDB; 3U7C; X-ray; 0.93 A; A=1-260.
DR PDB; 3V2J; X-ray; 1.70 A; A=1-260.
DR PDB; 3V2M; X-ray; 1.47 A; A=1-260.
DR PDB; 3V3F; X-ray; 2.00 A; A=1-260.
DR PDB; 3V3G; X-ray; 1.56 A; B=1-260.
DR PDB; 3V3H; X-ray; 1.85 A; B=1-260.
DR PDB; 3V3I; X-ray; 1.73 A; B=1-260.
DR PDB; 3V3J; X-ray; 1.63 A; A=1-260.
DR PDB; 3V5G; X-ray; 1.50 A; A=1-260.
DR PDB; 3V7X; X-ray; 1.03 A; A=2-260.
DR PDB; 3VBD; X-ray; 1.05 A; A=2-260.
DR PDB; 3ZP9; X-ray; 1.31 A; A=1-260.
DR PDB; 4BCW; X-ray; 1.50 A; A=4-260.
DR PDB; 4CA2; X-ray; 2.10 A; A=2-260.
DR PDB; 4CAC; X-ray; 2.20 A; A=2-260.
DR PDB; 4DZ7; X-ray; 1.49 A; A=1-260.
DR PDB; 4DZ9; X-ray; 1.49 A; A=1-260.
DR PDB; 4E3D; X-ray; 1.60 A; A=1-260.
DR PDB; 4E3F; X-ray; 1.50 A; A=1-260.
DR PDB; 4E3G; X-ray; 1.55 A; A=1-260.
DR PDB; 4E3H; X-ray; 1.50 A; A=1-260.
DR PDB; 4E49; X-ray; 1.45 A; A=1-260.
DR PDB; 4E4A; X-ray; 1.45 A; A=1-260.
DR PDB; 4E5Q; X-ray; 1.70 A; A=1-260.
DR PDB; 4FIK; X-ray; 1.20 A; A=1-260.
DR PDB; 4FL7; X-ray; 1.85 A; A=2-260.
DR PDB; 4FPT; X-ray; 0.98 A; A=1-260.
DR PDB; 4FRC; X-ray; 0.98 A; A=1-260.
DR PDB; 4FU5; X-ray; 0.98 A; A=1-260.
DR PDB; 4FVN; X-ray; 1.05 A; A=1-260.
DR PDB; 4FVO; X-ray; 1.05 A; A=1-260.
DR PDB; 4G0C; Neutron; 2.00 A; A=4-260.
DR PDB; 4GGE; X-ray; 1.47 A; A=1-260.
DR PDB; 4GL1; X-ray; 1.50 A; X=1-260.
DR PDB; 4HBA; X-ray; 1.76 A; A=1-260.
DR PDB; 4HEW; X-ray; 1.70 A; A=1-260.
DR PDB; 4HEY; X-ray; 1.45 A; A=1-260.
DR PDB; 4HEZ; X-ray; 1.34 A; A=1-260.
DR PDB; 4HF3; X-ray; 1.15 A; A=1-260.
DR PDB; 4HT0; X-ray; 1.60 A; A=1-260.
DR PDB; 4IDR; X-ray; 1.60 A; X=3-260.
DR PDB; 4ILX; X-ray; 1.60 A; A=4-260.
DR PDB; 4JS6; X-ray; 1.55 A; A=1-260.
DR PDB; 4JSA; X-ray; 1.50 A; A=1-260.
DR PDB; 4JSS; X-ray; 1.50 A; A=1-260.
DR PDB; 4JSW; X-ray; 1.90 A; A=1-260.
DR PDB; 4JSZ; X-ray; 1.90 A; A=1-260.
DR PDB; 4KAP; X-ray; 1.45 A; A=5-260.
DR PDB; 4KNI; X-ray; 1.80 A; A=1-260.
DR PDB; 4KNJ; X-ray; 2.00 A; A=1-260.
DR PDB; 4LP6; X-ray; 2.15 A; A/B=1-260.
DR PDB; 4M2R; X-ray; 1.99 A; A=4-260.
DR PDB; 4M2U; X-ray; 2.00 A; A=4-260.
DR PDB; 4M2V; X-ray; 1.72 A; A=4-260.
DR PDB; 4M2W; X-ray; 1.66 A; A=4-260.
DR PDB; 4MO8; X-ray; 1.85 A; A=1-260.
DR PDB; 5CA2; X-ray; 2.10 A; A=2-260.
DR PDB; 5CAC; X-ray; 2.20 A; A=2-260.
DR PDB; 6CA2; X-ray; 2.50 A; A=2-260.
DR PDB; 7CA2; X-ray; 2.40 A; A=2-260.
DR PDB; 8CA2; X-ray; 2.40 A; A=2-260.
DR PDB; 9CA2; X-ray; 2.80 A; A=2-260.
DR PDBsum; 12CA; -.
DR PDBsum; 1A42; -.
DR PDBsum; 1AM6; -.
DR PDBsum; 1AVN; -.
DR PDBsum; 1BCD; -.
DR PDBsum; 1BIC; -.
DR PDBsum; 1BN1; -.
DR PDBsum; 1BN3; -.
DR PDBsum; 1BN4; -.
DR PDBsum; 1BNM; -.
DR PDBsum; 1BNN; -.
DR PDBsum; 1BNQ; -.
DR PDBsum; 1BNT; -.
DR PDBsum; 1BNU; -.
DR PDBsum; 1BNV; -.
DR PDBsum; 1BNW; -.
DR PDBsum; 1BV3; -.
DR PDBsum; 1CA2; -.
DR PDBsum; 1CA3; -.
DR PDBsum; 1CAH; -.
DR PDBsum; 1CAI; -.
DR PDBsum; 1CAJ; -.
DR PDBsum; 1CAK; -.
DR PDBsum; 1CAL; -.
DR PDBsum; 1CAM; -.
DR PDBsum; 1CAN; -.
DR PDBsum; 1CAO; -.
DR PDBsum; 1CAY; -.
DR PDBsum; 1CAZ; -.
DR PDBsum; 1CCS; -.
DR PDBsum; 1CCT; -.
DR PDBsum; 1CCU; -.
DR PDBsum; 1CIL; -.
DR PDBsum; 1CIM; -.
DR PDBsum; 1CIN; -.
DR PDBsum; 1CNB; -.
DR PDBsum; 1CNC; -.
DR PDBsum; 1CNG; -.
DR PDBsum; 1CNH; -.
DR PDBsum; 1CNI; -.
DR PDBsum; 1CNJ; -.
DR PDBsum; 1CNK; -.
DR PDBsum; 1CNW; -.
DR PDBsum; 1CNX; -.
DR PDBsum; 1CNY; -.
DR PDBsum; 1CRA; -.
DR PDBsum; 1CVA; -.
DR PDBsum; 1CVB; -.
DR PDBsum; 1CVC; -.
DR PDBsum; 1CVD; -.
DR PDBsum; 1CVE; -.
DR PDBsum; 1CVF; -.
DR PDBsum; 1CVH; -.
DR PDBsum; 1DCA; -.
DR PDBsum; 1DCB; -.
DR PDBsum; 1EOU; -.
DR PDBsum; 1F2W; -.
DR PDBsum; 1FQL; -.
DR PDBsum; 1FQM; -.
DR PDBsum; 1FQN; -.
DR PDBsum; 1FQR; -.
DR PDBsum; 1FR4; -.
DR PDBsum; 1FR7; -.
DR PDBsum; 1FSN; -.
DR PDBsum; 1FSQ; -.
DR PDBsum; 1FSR; -.
DR PDBsum; 1G0E; -.
DR PDBsum; 1G0F; -.
DR PDBsum; 1G1D; -.
DR PDBsum; 1G3Z; -.
DR PDBsum; 1G45; -.
DR PDBsum; 1G46; -.
DR PDBsum; 1G48; -.
DR PDBsum; 1G4J; -.
DR PDBsum; 1G4O; -.
DR PDBsum; 1G52; -.
DR PDBsum; 1G53; -.
DR PDBsum; 1G54; -.
DR PDBsum; 1H4N; -.
DR PDBsum; 1H9N; -.
DR PDBsum; 1H9Q; -.
DR PDBsum; 1HCA; -.
DR PDBsum; 1HEA; -.
DR PDBsum; 1HEB; -.
DR PDBsum; 1HEC; -.
DR PDBsum; 1HED; -.
DR PDBsum; 1HVA; -.
DR PDBsum; 1I8Z; -.
DR PDBsum; 1I90; -.
DR PDBsum; 1I91; -.
DR PDBsum; 1I9L; -.
DR PDBsum; 1I9M; -.
DR PDBsum; 1I9N; -.
DR PDBsum; 1I9O; -.
DR PDBsum; 1I9P; -.
DR PDBsum; 1I9Q; -.
DR PDBsum; 1IF4; -.
DR PDBsum; 1IF5; -.
DR PDBsum; 1IF6; -.
DR PDBsum; 1IF7; -.
DR PDBsum; 1IF8; -.
DR PDBsum; 1IF9; -.
DR PDBsum; 1KWQ; -.
DR PDBsum; 1KWR; -.
DR PDBsum; 1LG5; -.
DR PDBsum; 1LG6; -.
DR PDBsum; 1LGD; -.
DR PDBsum; 1LUG; -.
DR PDBsum; 1LZV; -.
DR PDBsum; 1MOO; -.
DR PDBsum; 1MUA; -.
DR PDBsum; 1OKL; -.
DR PDBsum; 1OKM; -.
DR PDBsum; 1OKN; -.
DR PDBsum; 1OQ5; -.
DR PDBsum; 1RAY; -.
DR PDBsum; 1RAZ; -.
DR PDBsum; 1RZA; -.
DR PDBsum; 1RZB; -.
DR PDBsum; 1RZC; -.
DR PDBsum; 1RZD; -.
DR PDBsum; 1RZE; -.
DR PDBsum; 1T9N; -.
DR PDBsum; 1TB0; -.
DR PDBsum; 1TBT; -.
DR PDBsum; 1TE3; -.
DR PDBsum; 1TEQ; -.
DR PDBsum; 1TEU; -.
DR PDBsum; 1TG3; -.
DR PDBsum; 1TG9; -.
DR PDBsum; 1TH9; -.
DR PDBsum; 1THK; -.
DR PDBsum; 1TTM; -.
DR PDBsum; 1UGA; -.
DR PDBsum; 1UGB; -.
DR PDBsum; 1UGC; -.
DR PDBsum; 1UGD; -.
DR PDBsum; 1UGE; -.
DR PDBsum; 1UGF; -.
DR PDBsum; 1UGG; -.
DR PDBsum; 1XEG; -.
DR PDBsum; 1XEV; -.
DR PDBsum; 1XPZ; -.
DR PDBsum; 1XQ0; -.
DR PDBsum; 1YDA; -.
DR PDBsum; 1YDB; -.
DR PDBsum; 1YDC; -.
DR PDBsum; 1YDD; -.
DR PDBsum; 1YO0; -.
DR PDBsum; 1YO1; -.
DR PDBsum; 1YO2; -.
DR PDBsum; 1Z9Y; -.
DR PDBsum; 1ZE8; -.
DR PDBsum; 1ZFK; -.
DR PDBsum; 1ZFQ; -.
DR PDBsum; 1ZGE; -.
DR PDBsum; 1ZGF; -.
DR PDBsum; 1ZH9; -.
DR PDBsum; 1ZSA; -.
DR PDBsum; 1ZSB; -.
DR PDBsum; 1ZSC; -.
DR PDBsum; 2ABE; -.
DR PDBsum; 2AW1; -.
DR PDBsum; 2AX2; -.
DR PDBsum; 2CA2; -.
DR PDBsum; 2CBA; -.
DR PDBsum; 2CBB; -.
DR PDBsum; 2CBC; -.
DR PDBsum; 2CBD; -.
DR PDBsum; 2CBE; -.
DR PDBsum; 2EU2; -.
DR PDBsum; 2EU3; -.
DR PDBsum; 2EZ7; -.
DR PDBsum; 2F14; -.
DR PDBsum; 2FMG; -.
DR PDBsum; 2FMZ; -.
DR PDBsum; 2FNK; -.
DR PDBsum; 2FNM; -.
DR PDBsum; 2FNN; -.
DR PDBsum; 2FOQ; -.
DR PDBsum; 2FOS; -.
DR PDBsum; 2FOU; -.
DR PDBsum; 2FOV; -.
DR PDBsum; 2GD8; -.
DR PDBsum; 2GEH; -.
DR PDBsum; 2H15; -.
DR PDBsum; 2H4N; -.
DR PDBsum; 2HD6; -.
DR PDBsum; 2HKK; -.
DR PDBsum; 2HL4; -.
DR PDBsum; 2HNC; -.
DR PDBsum; 2HOC; -.
DR PDBsum; 2ILI; -.
DR PDBsum; 2NNG; -.
DR PDBsum; 2NNO; -.
DR PDBsum; 2NNS; -.
DR PDBsum; 2NNV; -.
DR PDBsum; 2NWO; -.
DR PDBsum; 2NWP; -.
DR PDBsum; 2NWY; -.
DR PDBsum; 2NWZ; -.
DR PDBsum; 2NXR; -.
DR PDBsum; 2NXS; -.
DR PDBsum; 2NXT; -.
DR PDBsum; 2O4Z; -.
DR PDBsum; 2OSF; -.
DR PDBsum; 2OSM; -.
DR PDBsum; 2POU; -.
DR PDBsum; 2POV; -.
DR PDBsum; 2POW; -.
DR PDBsum; 2Q1B; -.
DR PDBsum; 2Q1Q; -.
DR PDBsum; 2Q38; -.
DR PDBsum; 2QO8; -.
DR PDBsum; 2QOA; -.
DR PDBsum; 2QP6; -.
DR PDBsum; 2VVA; -.
DR PDBsum; 2VVB; -.
DR PDBsum; 2WD2; -.
DR PDBsum; 2WD3; -.
DR PDBsum; 2WEG; -.
DR PDBsum; 2WEH; -.
DR PDBsum; 2WEJ; -.
DR PDBsum; 2WEO; -.
DR PDBsum; 2X7S; -.
DR PDBsum; 2X7T; -.
DR PDBsum; 2X7U; -.
DR PDBsum; 3B4F; -.
DR PDBsum; 3BET; -.
DR PDBsum; 3BL0; -.
DR PDBsum; 3BL1; -.
DR PDBsum; 3C7P; -.
DR PDBsum; 3CA2; -.
DR PDBsum; 3CAJ; -.
DR PDBsum; 3CYU; -.
DR PDBsum; 3D8W; -.
DR PDBsum; 3D92; -.
DR PDBsum; 3D93; -.
DR PDBsum; 3D9Z; -.
DR PDBsum; 3DAZ; -.
DR PDBsum; 3DBU; -.
DR PDBsum; 3DC3; -.
DR PDBsum; 3DC9; -.
DR PDBsum; 3DCC; -.
DR PDBsum; 3DCS; -.
DR PDBsum; 3DCW; -.
DR PDBsum; 3DD0; -.
DR PDBsum; 3DD8; -.
DR PDBsum; 3DV7; -.
DR PDBsum; 3DVB; -.
DR PDBsum; 3DVC; -.
DR PDBsum; 3DVD; -.
DR PDBsum; 3EFI; -.
DR PDBsum; 3EFT; -.
DR PDBsum; 3F4X; -.
DR PDBsum; 3F8E; -.
DR PDBsum; 3FFP; -.
DR PDBsum; 3GZ0; -.
DR PDBsum; 3HFP; -.
DR PDBsum; 3HKN; -.
DR PDBsum; 3HKQ; -.
DR PDBsum; 3HKT; -.
DR PDBsum; 3HKU; -.
DR PDBsum; 3HLJ; -.
DR PDBsum; 3HS4; -.
DR PDBsum; 3IBI; -.
DR PDBsum; 3IBL; -.
DR PDBsum; 3IBN; -.
DR PDBsum; 3IBU; -.
DR PDBsum; 3IEO; -.
DR PDBsum; 3IGP; -.
DR PDBsum; 3K2F; -.
DR PDBsum; 3K34; -.
DR PDBsum; 3K7K; -.
DR PDBsum; 3KIG; -.
DR PDBsum; 3KKX; -.
DR PDBsum; 3KNE; -.
DR PDBsum; 3KOI; -.
DR PDBsum; 3KOK; -.
DR PDBsum; 3KON; -.
DR PDBsum; 3KS3; -.
DR PDBsum; 3KWA; -.
DR PDBsum; 3L14; -.
DR PDBsum; 3M04; -.
DR PDBsum; 3M14; -.
DR PDBsum; 3M1J; -.
DR PDBsum; 3M1K; -.
DR PDBsum; 3M1Q; -.
DR PDBsum; 3M1W; -.
DR PDBsum; 3M2N; -.
DR PDBsum; 3M2X; -.
DR PDBsum; 3M2Y; -.
DR PDBsum; 3M2Z; -.
DR PDBsum; 3M3X; -.
DR PDBsum; 3M40; -.
DR PDBsum; 3M5E; -.
DR PDBsum; 3M5S; -.
DR PDBsum; 3M5T; -.
DR PDBsum; 3M67; -.
DR PDBsum; 3M96; -.
DR PDBsum; 3M98; -.
DR PDBsum; 3MHC; -.
DR PDBsum; 3MHI; -.
DR PDBsum; 3MHL; -.
DR PDBsum; 3MHM; -.
DR PDBsum; 3MHO; -.
DR PDBsum; 3ML2; -.
DR PDBsum; 3MMF; -.
DR PDBsum; 3MNA; -.
DR PDBsum; 3MNH; -.
DR PDBsum; 3MNI; -.
DR PDBsum; 3MNJ; -.
DR PDBsum; 3MNK; -.
DR PDBsum; 3MNU; -.
DR PDBsum; 3MWO; -.
DR PDBsum; 3MYQ; -.
DR PDBsum; 3MZC; -.
DR PDBsum; 3N0N; -.
DR PDBsum; 3N2P; -.
DR PDBsum; 3N3J; -.
DR PDBsum; 3N4B; -.
DR PDBsum; 3NB5; -.
DR PDBsum; 3NI5; -.
DR PDBsum; 3NJ9; -.
DR PDBsum; 3OIK; -.
DR PDBsum; 3OIL; -.
DR PDBsum; 3OIM; -.
DR PDBsum; 3OKU; -.
DR PDBsum; 3OKV; -.
DR PDBsum; 3OY0; -.
DR PDBsum; 3OYQ; -.
DR PDBsum; 3OYS; -.
DR PDBsum; 3P3H; -.
DR PDBsum; 3P3J; -.
DR PDBsum; 3P44; -.
DR PDBsum; 3P4V; -.
DR PDBsum; 3P55; -.
DR PDBsum; 3P58; -.
DR PDBsum; 3P5A; -.
DR PDBsum; 3P5L; -.
DR PDBsum; 3PJJ; -.
DR PDBsum; 3PO6; -.
DR PDBsum; 3PYK; -.
DR PDBsum; 3QYK; -.
DR PDBsum; 3R16; -.
DR PDBsum; 3R17; -.
DR PDBsum; 3RG3; -.
DR PDBsum; 3RG4; -.
DR PDBsum; 3RGE; -.
DR PDBsum; 3RJ7; -.
DR PDBsum; 3RLD; -.
DR PDBsum; 3RYJ; -.
DR PDBsum; 3RYV; -.
DR PDBsum; 3RYX; -.
DR PDBsum; 3RYY; -.
DR PDBsum; 3RYZ; -.
DR PDBsum; 3RZ0; -.
DR PDBsum; 3RZ1; -.
DR PDBsum; 3RZ5; -.
DR PDBsum; 3RZ7; -.
DR PDBsum; 3RZ8; -.
DR PDBsum; 3S71; -.
DR PDBsum; 3S72; -.
DR PDBsum; 3S73; -.
DR PDBsum; 3S74; -.
DR PDBsum; 3S75; -.
DR PDBsum; 3S76; -.
DR PDBsum; 3S77; -.
DR PDBsum; 3S78; -.
DR PDBsum; 3S8X; -.
DR PDBsum; 3S9T; -.
DR PDBsum; 3SAP; -.
DR PDBsum; 3SAX; -.
DR PDBsum; 3SBH; -.
DR PDBsum; 3SBI; -.
DR PDBsum; 3T5U; -.
DR PDBsum; 3T5Z; -.
DR PDBsum; 3T82; -.
DR PDBsum; 3T83; -.
DR PDBsum; 3T84; -.
DR PDBsum; 3T85; -.
DR PDBsum; 3TMJ; -.
DR PDBsum; 3TVN; -.
DR PDBsum; 3TVO; -.
DR PDBsum; 3U3A; -.
DR PDBsum; 3U45; -.
DR PDBsum; 3U47; -.
DR PDBsum; 3U7C; -.
DR PDBsum; 3V2J; -.
DR PDBsum; 3V2M; -.
DR PDBsum; 3V3F; -.
DR PDBsum; 3V3G; -.
DR PDBsum; 3V3H; -.
DR PDBsum; 3V3I; -.
DR PDBsum; 3V3J; -.
DR PDBsum; 3V5G; -.
DR PDBsum; 3V7X; -.
DR PDBsum; 3VBD; -.
DR PDBsum; 3ZP9; -.
DR PDBsum; 4BCW; -.
DR PDBsum; 4CA2; -.
DR PDBsum; 4CAC; -.
DR PDBsum; 4DZ7; -.
DR PDBsum; 4DZ9; -.
DR PDBsum; 4E3D; -.
DR PDBsum; 4E3F; -.
DR PDBsum; 4E3G; -.
DR PDBsum; 4E3H; -.
DR PDBsum; 4E49; -.
DR PDBsum; 4E4A; -.
DR PDBsum; 4E5Q; -.
DR PDBsum; 4FIK; -.
DR PDBsum; 4FL7; -.
DR PDBsum; 4FPT; -.
DR PDBsum; 4FRC; -.
DR PDBsum; 4FU5; -.
DR PDBsum; 4FVN; -.
DR PDBsum; 4FVO; -.
DR PDBsum; 4G0C; -.
DR PDBsum; 4GGE; -.
DR PDBsum; 4GL1; -.
DR PDBsum; 4HBA; -.
DR PDBsum; 4HEW; -.
DR PDBsum; 4HEY; -.
DR PDBsum; 4HEZ; -.
DR PDBsum; 4HF3; -.
DR PDBsum; 4HT0; -.
DR PDBsum; 4IDR; -.
DR PDBsum; 4ILX; -.
DR PDBsum; 4JS6; -.
DR PDBsum; 4JSA; -.
DR PDBsum; 4JSS; -.
DR PDBsum; 4JSW; -.
DR PDBsum; 4JSZ; -.
DR PDBsum; 4KAP; -.
DR PDBsum; 4KNI; -.
DR PDBsum; 4KNJ; -.
DR PDBsum; 4LP6; -.
DR PDBsum; 4M2R; -.
DR PDBsum; 4M2U; -.
DR PDBsum; 4M2V; -.
DR PDBsum; 4M2W; -.
DR PDBsum; 4MO8; -.
DR PDBsum; 5CA2; -.
DR PDBsum; 5CAC; -.
DR PDBsum; 6CA2; -.
DR PDBsum; 7CA2; -.
DR PDBsum; 8CA2; -.
DR PDBsum; 9CA2; -.
DR ProteinModelPortal; P00918; -.
DR SMR; P00918; 3-260.
DR IntAct; P00918; 5.
DR MINT; MINT-1367766; -.
DR STRING; 9606.ENSP00000285379; -.
DR BindingDB; P00918; -.
DR ChEMBL; CHEMBL205; -.
DR DrugBank; DB00819; Acetazolamide.
DR DrugBank; DB00436; Bendroflumethiazide.
DR DrugBank; DB00562; Benzthiazide.
DR DrugBank; DB01194; Brinzolamide.
DR DrugBank; DB00880; Chlorothiazide.
DR DrugBank; DB00606; Cyclothiazide.
DR DrugBank; DB01119; Diazoxide.
DR DrugBank; DB00869; Dorzolamide.
DR DrugBank; DB01031; Ethinamate.
DR DrugBank; DB00999; Hydrochlorothiazide.
DR DrugBank; DB00774; Hydroflumethiazide.
DR DrugBank; DB00232; Methyclothiazide.
DR DrugBank; DB01325; Quinethazone.
DR DrugBank; DB00273; Topiramate.
DR DrugBank; DB01021; Trichlormethiazide.
DR PhosphoSite; P00918; -.
DR DMDM; 115456; -.
DR OGP; P00918; -.
DR REPRODUCTION-2DPAGE; IPI00218414; -.
DR REPRODUCTION-2DPAGE; P00918; -.
DR UCD-2DPAGE; P00918; -.
DR PaxDb; P00918; -.
DR PeptideAtlas; P00918; -.
DR PRIDE; P00918; -.
DR DNASU; 760; -.
DR Ensembl; ENST00000285379; ENSP00000285379; ENSG00000104267.
DR GeneID; 760; -.
DR KEGG; hsa:760; -.
DR UCSC; uc003ydk.2; human.
DR CTD; 760; -.
DR GeneCards; GC08P086376; -.
DR HGNC; HGNC:1373; CA2.
DR HPA; CAB010102; -.
DR HPA; HPA001550; -.
DR MIM; 259730; phenotype.
DR MIM; 611492; gene.
DR neXtProt; NX_P00918; -.
DR Orphanet; 2785; Osteopetrosis with renal tubular acidosis.
DR PharmGKB; PA25989; -.
DR eggNOG; COG3338; -.
DR HOGENOM; HOG000112637; -.
DR HOVERGEN; HBG002837; -.
DR InParanoid; P00918; -.
DR KO; K01672; -.
DR OMA; DEANEAC; -.
DR OrthoDB; EOG7WMCK7; -.
DR BRENDA; 4.2.1.1; 2681.
DR Reactome; REACT_111217; Metabolism.
DR SABIO-RK; P00918; -.
DR ChiTaRS; CA2; human.
DR EvolutionaryTrace; P00918; -.
DR GeneWiki; Carbonic_anhydrase_II; -.
DR GenomeRNAi; 760; -.
DR NextBio; 3074; -.
DR PRO; PR:P00918; -.
DR ArrayExpress; P00918; -.
DR Bgee; P00918; -.
DR CleanEx; HS_CA2; -.
DR Genevestigator; P00918; -.
DR GO; GO:0045177; C:apical part of cell; IDA:UniProtKB.
DR GO; GO:0030424; C:axon; IEA:Ensembl.
DR GO; GO:0016323; C:basolateral plasma membrane; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IEA:Ensembl.
DR GO; GO:0005902; C:microvillus; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0004089; F:carbonate dehydratase activity; TAS:ProtInc.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0038166; P:angiotensin-mediated signaling pathway; IDA:UniProtKB.
DR GO; GO:0015701; P:bicarbonate transport; TAS:Reactome.
DR GO; GO:0015670; P:carbon dioxide transport; IEA:Ensembl.
DR GO; GO:0001822; P:kidney development; IEA:Ensembl.
DR GO; GO:0002009; P:morphogenesis of an epithelium; IEA:Ensembl.
DR GO; GO:0042475; P:odontogenesis of dentin-containing tooth; IEA:Ensembl.
DR GO; GO:0006730; P:one-carbon metabolic process; IEA:InterPro.
DR GO; GO:0045780; P:positive regulation of bone resorption; IEA:Ensembl.
DR GO; GO:0032849; P:positive regulation of cellular pH reduction; IEA:Ensembl.
DR GO; GO:2001150; P:positive regulation of dipeptide transmembrane transport; ISS:UniProtKB.
DR GO; GO:0045672; P:positive regulation of osteoclast differentiation; IEA:Ensembl.
DR GO; GO:0044070; P:regulation of anion transport; IDA:UniProtKB.
DR GO; GO:0051453; P:regulation of intracellular pH; ISS:UniProtKB.
DR GO; GO:0043627; P:response to estrogen stimulus; IEA:Ensembl.
DR GO; GO:0009268; P:response to pH; IEA:Ensembl.
DR GO; GO:0006950; P:response to stress; IEA:Ensembl.
DR GO; GO:0010043; P:response to zinc ion; IEA:Ensembl.
DR GO; GO:0046903; P:secretion; IEA:Ensembl.
DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome.
DR Gene3D; 3.10.200.10; -; 1.
DR InterPro; IPR018443; CA2/13.
DR InterPro; IPR001148; Carbonic_anhydrase_a.
DR InterPro; IPR023561; Carbonic_anhydrase_a-class.
DR InterPro; IPR018338; Carbonic_anhydrase_a-class_CS.
DR PANTHER; PTHR18952; PTHR18952; 1.
DR PANTHER; PTHR18952:SF31; PTHR18952:SF31; 1.
DR Pfam; PF00194; Carb_anhydrase; 1.
DR SMART; SM01057; Carb_anhydrase; 1.
DR SUPFAM; SSF51069; SSF51069; 1.
DR PROSITE; PS00162; ALPHA_CA_1; 1.
DR PROSITE; PS51144; ALPHA_CA_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cell membrane; Complete proteome;
KW Cytoplasm; Direct protein sequencing; Disease mutation; Lyase;
KW Membrane; Metal-binding; Osteopetrosis; Polymorphism;
KW Reference proteome; Zinc.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 260 Carbonic anhydrase 2.
FT /FTId=PRO_0000077418.
FT REGION 198 199 Substrate binding.
FT ACT_SITE 64 64
FT ACT_SITE 67 67
FT ACT_SITE 127 127
FT METAL 94 94 Zinc; catalytic.
FT METAL 96 96 Zinc; catalytic.
FT METAL 119 119 Zinc; catalytic.
FT BINDING 62 62 Activator.
FT BINDING 67 67 Activator.
FT BINDING 92 92 Activator.
FT MOD_RES 2 2 N-acetylserine.
FT VARIANT 18 18 K -> E (in Jogjakarta).
FT /FTId=VAR_001380.
FT VARIANT 92 92 Q -> P (in OPTB3; in Czechoslovakia).
FT /FTId=VAR_001381.
FT VARIANT 94 94 H -> Y (in OPTB3; partial loss of
FT activity).
FT /FTId=VAR_021009.
FT VARIANT 107 107 H -> Y (in OPTB3; frequent mutation).
FT /FTId=VAR_001382.
FT VARIANT 144 144 G -> R (in OPTB3; complete loss of
FT activity).
FT /FTId=VAR_021010.
FT VARIANT 236 236 P -> H (in Melbourne).
FT /FTId=VAR_001383.
FT VARIANT 252 252 N -> D (in dbSNP:rs2228063).
FT /FTId=VAR_001384.
FT MUTAGEN 5 5 W->A: Impaired activity, not rescued by
FT 4-methylimidazole (4-MI); when associated
FT with W-64.
FT MUTAGEN 7 7 Y->F: Enhanced activity.
FT MUTAGEN 7 7 Y->H: Reduced proton transfer rate.
FT MUTAGEN 62 62 N->A: Reduced activity.
FT MUTAGEN 62 62 N->D: Strongly reduced activity.
FT MUTAGEN 62 62 N->H: Reduced proton transfer; when
FT associated with A-64.
FT MUTAGEN 62 62 N->L: Reduced activity.
FT MUTAGEN 62 62 N->T: Reduced activity.
FT MUTAGEN 62 62 N->V: Reduced activity.
FT MUTAGEN 64 64 H->A: Reduced CO(2) hydrase activity,
FT rescued by 4-methylimidazole (4-MI).
FT Reduced proton transfer; when associated
FT with H-62. Enhanced proton transfer; when
FT associated with H-67. Enhanced proton
FT transfer capacity; when associated with
FT H-99.
FT MUTAGEN 64 64 H->G: Impaired activity, not rescued by
FT 4-methylimidazole (4-MI).
FT MUTAGEN 64 64 H->W: Impaired activity, rescued by 4-
FT methylimidazole (4-MI). Impaired
FT activity, not rescued by 4-
FT methylimidazole (4-MI); when associated
FT with A-5.
FT MUTAGEN 65 65 A->F: Reduced activity.
FT MUTAGEN 65 65 A->H,L,S: Normal activity.
FT MUTAGEN 67 67 N->H: Enhanced proton transfer; when
FT associated with A-64.
FT MUTAGEN 67 67 N->L: Reduced activity.
FT MUTAGEN 67 67 N->Q: Normal activity.
FT MUTAGEN 94 94 H->C,D,E,N,Q: Strongly reduced CO(2)
FT hydrase and p-nitrophenyl acetate
FT esterase activities, impaired stability
FT of zinc binding.
FT MUTAGEN 106 106 E->A,Q: Strongly reduced CO(2) hydrase
FT activity.
FT MUTAGEN 106 106 E->D: Normal CO(2) hydrase activity.
FT MUTAGEN 117 117 E->Q: Strongly reduced activity and
FT sulfonamide affinity.
FT MUTAGEN 119 119 H->D,N,Q: Reduced activity.
FT MUTAGEN 119 119 H->E: Strongly reduced activity.
FT MUTAGEN 121 121 V->A,G,I,L,S: Reduced CO(2) hydrase and
FT p-nitrophenyl acetate esterase
FT activities.
FT MUTAGEN 121 121 V->K,R: Strongly reduced CO(2) hydrase
FT and p-nitrophenyl acetate esterase
FT activities.
FT MUTAGEN 142 142 V->F,Y: Strongly impaired activity.
FT MUTAGEN 142 142 V->G: Weakly impaired activity.
FT MUTAGEN 142 142 V->H: Impaired activity.
FT MUTAGEN 197 197 L->A: Reduced CO(2) hydrase activity.
FT MUTAGEN 197 197 L->E,H,R: Strongly reduced CO(2) hydrase
FT activity.
FT MUTAGEN 197 197 L->F: Normal activity.
FT MUTAGEN 198 198 T->A,C,H,P: Strongly reduced activity.
FT MUTAGEN 198 198 T->D,E: Strongly reduced activity, but
FT enhanced zinc affinity.
FT MUTAGEN 198 198 T->S,V: Reduced activity.
FT MUTAGEN 199 199 T->H: Higher affinity for bicarbonate.
FT Enhanced proton transfer capacity; when
FT associated with A-64.
FT MUTAGEN 199 199 T->S: Enhanced p-nitrophenyl acetate
FT esterase activity, but normal CO(2)
FT hydrase activity.
FT MUTAGEN 201 201 P->A: Normal CO(2) hydrase activity, but
FT impaired stability.
FT CONFLICT 179 180 DP -> AA (in Ref. 6; AAH11949).
FT TURN 9 11
FT TURN 13 15
FT HELIX 16 18
FT HELIX 21 24
FT STRAND 25 27
FT STRAND 31 33
FT TURN 35 37
FT STRAND 38 40
FT STRAND 42 44
FT STRAND 45 50
FT STRAND 56 61
FT STRAND 63 70
FT STRAND 73 75
FT STRAND 77 82
FT STRAND 88 97
FT STRAND 106 109
FT STRAND 115 124
FT HELIX 125 127
FT HELIX 130 133
FT STRAND 139 151
FT HELIX 154 156
FT HELIX 157 162
FT HELIX 163 165
FT STRAND 172 174
FT HELIX 180 183
FT STRAND 190 195
FT STRAND 206 213
FT STRAND 215 217
FT HELIX 219 225
FT STRAND 229 231
FT STRAND 233 235
FT STRAND 256 258
SQ SEQUENCE 260 AA; 29246 MW; 2EC2BB7548F10558 CRC64;
MSHHWGYGKH NGPEHWHKDF PIAKGERQSP VDIDTHTAKY DPSLKPLSVS YDQATSLRIL
NNGHAFNVEF DDSQDKAVLK GGPLDGTYRL IQFHFHWGSL DGQGSEHTVD KKKYAAELHL
VHWNTKYGDF GKAVQQPDGL AVLGIFLKVG SAKPGLQKVV DVLDSIKTKG KSADFTNFDP
RGLLPESLDY WTYPGSLTTP PLLECVTWIV LKEPISVSSE QVLKFRKLNF NGEGEPEELM
VDNWRPAQPL KNRQIKASFK
//
MIM
259730
*RECORD*
*FIELD* NO
259730
*FIELD* TI
#259730 OSTEOPETROSIS, AUTOSOMAL RECESSIVE 3; OPTB3
;;OSTEOPETROSIS WITH RENAL TUBULAR ACIDOSIS;;
read moreCARBONIC ANHYDRASE II DEFICIENCY;;
GUIBAUD-VAINSEL SYNDROME;;
MARBLE BRAIN DISEASE
*FIELD* TX
A number sign (#) is used with this entry because this form of autosomal
recessive osteopetrosis is caused by homozygous or compound heterozygous
mutation in the gene encoding carbonic anhydrase II (CA2; 611492) on
chromosome 8q22.
For a general phenotypic description and a discussion of genetic
heterogeneity of autosomal recessive osteopetrosis, see OPTB1 (259700).
CLINICAL FEATURES
Sly et al. (1972) described 3 sisters, aged 22, 17, and 15 years, born
to normal unrelated North American parents, with a form of osteopetrosis
distinct from both the malignant form (see OPTB1, 259700) and the benign
autosomal dominant form (see OPTA1, 607634). The disorder was manifest
in the first 2 years because of fractures. Other features were short
stature, mental retardation, dental malocclusion, and visual impairment
from optic nerve compression. Mild anemia in infancy improved later and
radiographic features of osteopetrosis improved some at puberty. Serum
acid phosphatase was elevated and electrolyte changes suggested mild
tubular acidosis. Whyte et al. (1980) provided a definitive report of
these sibs. During adolescence basal ganglion calcification developed in
2. Renal tubular acidosis (type I) was diagnosed in each in early
adulthood. Electron microscopy of bone suggested that osteoclasts failed
to form 'ruffled membranes' characteristic of active bone resorbing
cells. Chronic systemic acidosis may have ameliorated the skeletal
manifestations.
Guibaud et al. (1972) described 2 brothers with renal tubular acidosis
and mild osteopetrosis. The unaffected parents, from North Africa, were
cousins. Ohlsson et al. (1980) observed the syndrome, which they
referred to as marble brain disease, in children of 3 Saudi families.
They had striking facial similarities and cerebral calcifications.
Bourke et al. (1981) observed this syndrome in 2 Kuwaiti Bedouin sibs.
One sib showed basal ganglion calcification and mental subnormality. The
major clinical manifestation in both was periodic hypokalemic paresis.
Consanguinity was present in 9 of 12 pedigrees reported by Sly et al.
(1985). More than half the known cases have been in families from
Kuwait, Saudi Arabia, and North Africa. Ohlsson et al. (1986) described
the findings in 4 new Saudi Arabian cases from 2 families, including the
first description in a neonate. They reviewed the 17 previously reported
cases. Cochat et al. (1987) added a case and reviewed the findings in 30
reported patients. Al Rajeh et al. (1988) described 2 affected sisters
in a Saudi Arabian family.
Strisciuglio et al. (1990) described 3 affected Italian sibs, the
offspring of first cousins once removed. They had osteopetrosis with
fractures and severe mental retardation. Whereas most previous patients
had a mixed (proximal and distal) renal tubular acidosis, these patients
had only proximal tubular acidosis.
Aramaki et al. (1993) reported in detail the findings in 3 unrelated
Japanese patients with CA II deficiency. Two of the 3 were born of
first-cousin parents. All exhibited poor activity and poor appetite in
the neonatal period and then developed psychomotor retardation. Two of
them were diagnosed as having osteopetrosis at 10 months and 36 years of
age, respectively, and the third as having osteomalacia at 28 years of
age. All 3 had recurrent episodes of muscle weakness. Their parents
exhibited approximately 50% normal levels of CA II activity in protein.
The development of osteomalacia was considered to be related to the
renal tubular acidosis.
PATHOGENESIS
Sly et al. (1983) were prompted to examine carbonic anhydrase (CA) in
this disorder because sulfonamide inhibitors of CA can produce renal
tubular acidosis and block the parathormone-induced release of calcium
from bone. Although the relationship of CA deficiency to brain
calcification was unclear, it was known that one CA, CA II, is present
in brain and that CA inhibitors reduce CSF production and affect
electric activity of the brain. CA II is the one of the 3 CAs that is
expressed in both brain and kidney. Since it also is expressed in the
red cell, Sly et al. (1983) could study CA II in this tissue of their
patients; they found very low levels in affected persons and
intermediate levels in obligatory heterozygotes. The results indicate a
role of CA II in osteoclast function and bone resorption. The RTA in
this disorder is a hybrid of a mild proximal and prominent distal type.
CA II is the only cytosolic isozyme in the kidney. Red cell CA I
(114800) has been found to be normal in distal RTA.
POPULATION GENETICS
Fathallah et al. (1997) traced the origin of this disorder in 24
Tunisian families with CA II deficiency. All were descended from a
common ancestor who emigrated from the Arabic Peninsula to North Africa
in the 10th century.
MOLECULAR GENETICS
Venta et al. (1990, 1991) sequenced the CA2 gene in a patient with
osteopetrosis and renal tubular acidosis from the consanguineous Belgian
family first described by Vainsel et al. (1972) and identified
homozygosity for a missense mutation (H107Y; 611492.0004).
Roth et al. (1992) analyzed the molecular basis of carbonic anhydrase II
deficiency in the American family in which the association of CA2
deficiency with a clinical syndrome was first recognized by Sly et al.
(1972). The 3 affected sisters were found to be compound heterozygotes
for a maternally inherited H107Y mutation (611492.0004) and a paternally
inherited splice site mutation (611492.0005). Roth et al. (1992)
suggested that residual activity of the H107Y mutant enzyme,
demonstrated in expression studies in bacteria, might explain the
absence of mental retardation and relatively mild phenotype in affected
members of this family.
Hu et al. (1992) pointed out that of the 39 reported cases of carbonic
anhydrase deficiency syndrome, 72% were patients from North Africa and
the Middle East countries, most, if not all, of whom were of Arabic
descent. They showed that members of 6 unrelated Arabic kindreds were in
5 instances homozygous and in 1 instance heterozygous for a splice site
mutation in intron 3 of the CA2 gene (611492.0006). Called the 'Arabic
mutation,' it introduces a new Sau3A1 restriction site useful in
PCR-based diagnosis, carrier detection, and prenatal diagnosis. The
presence of mental retardation and relative infrequency of skeletal
fractures distinguish the clinical course of patients with the Arabic
mutation from that of American and Belgian patients with the H107Y
mutation.
In a 23-year-old Japanese woman previously reported by Aramaki et al.
(1993) ('patient 1' of pedigree A) with carbonic anhydrase II
deficiency, osteopetrosis, renal tubular acidosis, symmetrical cerebral
calcification, and mental retardation, Soda et al. (1995) found a Y40X
mutation in exon 2 of the CA2 gene resulting from a TAT-to-TAG
transversion.
Soda et al. (1996) identified the H107Y mutation in 2 unrelated Japanese
patients previously described by Aramaki et al. (1993), both born of
consanguineous parents, who had osteopetrosis and renal tubular acidosis
as well as severe mental retardation. The authors stated that the basis
for the more severe expression of the H107Y mutation, including mental
retardation, in Japanese patients was unclear.
Hu et al. (1997) identified 7 novel mutations in the CA2 gene in
patients with osteopetrosis and mental retardation or developmental
delay. All but 1 pair of Mexican sibs had renal tubular acidosis also.
Borthwick et al. (2003) described 2 consanguineous Turkish kindreds with
distal RTA and osteopetrosis. In affected members of 1 kindred, the
authors identified homozygosity for a frameshift mutation in the CA2
gene (611492.0008). The authors excluded defects in CA2 in the other
kindred, in which the proband had RTA and osteopetrosis but his sister
manifested only RTA with sensorineural hearing loss and never developed
osteopetrosis. In this kindred, Borthwick et al. (2003) found that the
osteopetrosis (259700) was the result of a homozygous deletion in the
TCIRG1 gene (604592.0007), whereas the distal RTA with hearing loss
(267300) was the result of a homozygous mutation in the ATP6V1B1 gene
(192132.0005). Borthwick et al. (2003) concluded that coinheritance of
these 2 rare recessive disorders created a phenocopy of CA2A deficiency
in this kindred, and commented that this case illustrates the importance
of clinical characterization of all affected members of a kindred.
*FIELD* SA
Sly (1989); Sundaram et al. (1986)
*FIELD* RF
1. Al Rajeh, S.; El Mouzan, M. I.; Ahlberg, A.; Ozaksoy, D.: The
syndrome of osteopetrosis, renal acidosis and cerebral calcification
in two sisters. Neuropediatrics 19: 162-165, 1988.
2. Aramaki, S.; Yoshida, I.; Yoshino, M.; Kondo, M.; Sato, Y.; Noda,
K.; Jo, R.; Okue, A.; Sai, N.; Yamashita, F.: Carbonic anhydrase
II deficiency in three unrelated Japanese patients. J. Inherit. Metab.
Dis. 16: 982-990, 1993.
3. Borthwick, K. J.; Kandemir, N.; Topaloglu, R.; Kornak, U.; Bakkaloglu,
A.; Yordam, N.; Ozen, S.; Mocan, H.; Shah, G. N.; Sly, W. S.; Karet,
F. E.: A phenocopy of CAII deficiency: a novel genetic explanation
for inherited infantile osteopetrosis with distal renal tubular acidosis. J.
Med. Genet. 40: 115-121, 2003.
4. Bourke, E.; Delaney, V. B.; Mosawi, M.; Reavey, P.; Weston, M.
: Renal tubular acidosis and osteopetrosis in siblings. Nephron 28:
268-272, 1981.
5. Cochat, P.; Loras-Duclaux, I.; Guibaud, P.: Deficit en anhydrase
carbonique II: osteopetrose, acidose renale tubulaire et calcifications
intracraniennes. Revue de la literature a'partir de trois observation. Pediatrie 42:
121-128, 1987.
6. Fathallah, D. M.; Bejaoui, M.; Lepaslier, D.; Chater, K.; Sly,
W. S.; Dellagi, K.: Carbonic anhydrase II (CA II) deficiency in Maghrebian
patients: evidence for founder effect and genomic recombination at
the CA II locus. Hum. Genet. 99: 634-637, 1997.
7. Guibaud, P.; Larbre, F.; Freycon, M. T.; Genoud, J.: Osteopetrose
et acidose renale tubulaire. Deux cas de cette association dans une
fratrie. Arch. Franc. Pediat. 29: 269-286, 1972.
8. Hu, P. Y.; Lim, E. J.; Ciccolella, J.; Strisciuglio, P.; Sly, W.
S.: Seven novel mutations in carbonic acid anhydrase II deficiency
syndrome identified by SSCP and direct sequencing analysis. Hum.
Mutat. 9: 383-387, 1997.
9. Hu, P. Y.; Roth, D. E.; Skaggs, L. A.; Venta, P. J.; Tashian, R.
E.; Guibaud, P.; Sly, W. S.: A splice junction mutation in intron
2 of the carbonic anhydrase II gene of osteopetrosis patients from
Arabic countries. Hum. Mutat. 1: 288-292, 1992.
10. Ohlsson, A.; Cumming, W. A.; Paul, A.; Sly, W. S.: Carbonic anhydrase
II deficiency syndrome: recessive osteopetrosis with renal tubular
acidosis and cerebral calcification. Pediatrics 77: 371-381, 1986.
11. Ohlsson, A.; Stark, G.; Sakati, N.: Marble brain disease: recessive
osteopetrosis, renal tubular acidosis and cerebral calcification in
three Saudi Arabian families. Dev. Med. Child Neurol. 22: 72-84,
1980.
12. Roth, D. E.; Venta, P. J.; Tashian, R. E.; Sly, W. S.: Molecular
basis of human carbonic anhydrase II deficiency. Proc. Nat. Acad.
Sci. 89: 1804-1808, 1992.
13. Sly, W. S.: The carbonic anhydrase II deficiency syndrome: osteopetrosis
with renal tubular acidosis and cerebral calcification.In: Scriver,
C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D.: The Metabolic Basis
of Inherited Disease. New York: McGraw-Hill (pub.) (6th ed.)
II: 1989. Pp. 2857-2866.
14. Sly, W. S.; Hewett-Emmett, D.; Whyte, M. P.; Yu, Y.-S. L.; Tashian,
R. E.: Carbonic anhydrase II deficiency identified as the primary
defect in the autosomal recessive syndrome of osteopetrosis with renal
tubular acidosis and cerebral calcification. Proc. Nat. Acad. Sci. 80:
2752-2756, 1983.
15. Sly, W. S.; Lang, R.; Avioli, L.; Haddad, J.; Lubowitz, H.; McAlister,
W.: Recessive osteopetrosis: new clinical phenotype. (Abstract) Am.
J. Hum. Genet. 24: 34A, 1972.
16. Sly, W. S.; Whyte, M. P.; Sundaram, V.; Tashian, R. E.; Hewett-Emmett,
D.; Guibaud, P.; Vainsel, M.; Baluarte, H. J.; Gruskin, A.; Al-Mosawi,
M.; Sakati, N.; Ohlsson, A.: Carbonic anhydrase II deficiency in
12 families with the autosomal recessive syndrome of osteopetrosis
with renal tubular acidosis and cerebral calcification. New Eng.
J. Med. 313: 139-145, 1985.
17. Soda, H.; Yukizane, S.; Yoshida, I.; Aramaki, S.; Kato, H.: Carbonic
anhydrase II deficiency in a Japanese patient produced by a nonsense
mutation (TAT-to-TAG) at tyr-40 in exon 2, (Y40X). Hum. Mutat. 5:
348-350, 1995.
18. Soda, H.; Yukizane, S.; Yoshida, I.; Koga, Y.; Aramaki, S.; Kato,
H.: A point mutation in exon 3 (his107-to-tyr) in two unrelated Japanese
patients with carbonic anhydrase II deficiency with central nervous
system involvement. Hum. Genet. 97: 435-437, 1996.
19. Strisciuglio, P.; Sartorio, R.; Pecoraro, C.; Lotito, F.; Sly,
W. S.: Variable clinical presentation of carbonic anhydrase deficiency:
evidence for heterogeneity? Europ. J. Pediat. 149: 337-340, 1990.
20. Sundaram, V.; Rumbolo, P.; Grubb, J.; Strisciuglio, P.; Sly, W.
S.: Carbonic anhydrase II deficiency: diagnosis and carrier detection
using differential enzyme inhibition and inactivation. Am. J. Hum.
Genet. 38: 125-136, 1986.
21. Vainsel, M.; Fondu, P.; Cadranel, S.; Rocmans, C.; Gepts, W.:
Osteopetrosis associated with proximal and distal tubular acidosis. Acta
Paediat. Scand. 61: 429-434, 1972.
22. Venta, P. J.; Welty, R. J.; Johnson, T. H.; Tashian, R. E.: Human
carbonic anhydrase II deficiency syndrome in a Belgium family appears
to be caused by a destabilizing amino acid substitution (107his-to-tyr).
(Abstract) Am. J. Hum. Genet. 47 (suppl.): A168, 1990.
23. Venta, P. J.; Welty, R. J.; Johnson, T. M.; Sly, W. S.; Tashian,
R. E.: Carbonic anhydrase II deficiency syndrome in a Belgian family
is caused by a point mutation at an invariant histidine residue (107his-to-tyr):
complete structure of the normal human CA II gene. Am. J. Hum. Genet. 49:
1082-1090, 1991.
24. Whyte, M. P.; Murphy, W. A.; Fallon, M. D.; Sly, W. S.; Teitelbaum,
S. L.; McAlister, W. H.; Avioli, L. V.: Osteopetrosis, renal tubular
acidosis and basal ganglia calcification in three sisters. Am. J.
Med. 69: 64-74, 1980.
*FIELD* CS
Growth:
Short stature
GI:
Hepatosplenomegaly
Skel:
Osteosclerosis
HEENT:
Cranial hyperostosis;
Dental malocclusion;
Visual impairment from optic nerve compression
Limbs:
Diaphyseal sclerosis
Neuro:
Basal ganglion calcification;
Normal intelligence or mental retardation
Heme:
Anemia;
Extramedullary hematopoiesis
Misc:
Onset in first 2 years with fractures
Lab:
Renal tubular acidosis, type I;
Elevated serum acid phosphatase;
Osteoclasts fail to form 'ruffled membranes' characteristic of active
bone resorbing cells;
Periodic hypokalemic paresis;
Carbonic anhydrase II defect
Inheritance:
Autosomal recessive
*FIELD* CN
Marla J. F. O'Neill - reorganized: 10/3/2007
Marla J. F. O'Neill - updated: 10/3/2007
Marla J. F. O'Neill - updated: 1/5/2005
Victor A. McKusick - updated: 4/16/1998
Ada Hamosh - updated: 7/10/1997
Victor A. McKusick - updated: 6/18/1997
Moyra Smith - updated: 3/13/1996
Orest Hurko - updated: 8/15/1995
*FIELD* CD
Victor A. McKusick: 6/4/1986
*FIELD* ED
alopez: 02/19/2013
carol: 10/10/2007
carol: 10/3/2007
terry: 4/4/2005
carol: 1/5/2005
carol: 3/17/2004
carol: 2/2/2004
carol: 3/1/2000
carol: 9/29/1999
carol: 9/28/1998
dkim: 9/10/1998
dholmes: 5/11/1998
carol: 5/2/1998
terry: 4/16/1998
alopez: 8/26/1997
alopez: 7/10/1997
jenny: 6/23/1997
mark: 6/18/1997
terry: 4/15/1996
mark: 3/13/1996
terry: 3/13/1996
mark: 3/13/1996
mark: 7/6/1995
pfoster: 8/17/1994
terry: 7/18/1994
jason: 7/12/1994
*RECORD*
*FIELD* NO
259730
*FIELD* TI
#259730 OSTEOPETROSIS, AUTOSOMAL RECESSIVE 3; OPTB3
;;OSTEOPETROSIS WITH RENAL TUBULAR ACIDOSIS;;
read moreCARBONIC ANHYDRASE II DEFICIENCY;;
GUIBAUD-VAINSEL SYNDROME;;
MARBLE BRAIN DISEASE
*FIELD* TX
A number sign (#) is used with this entry because this form of autosomal
recessive osteopetrosis is caused by homozygous or compound heterozygous
mutation in the gene encoding carbonic anhydrase II (CA2; 611492) on
chromosome 8q22.
For a general phenotypic description and a discussion of genetic
heterogeneity of autosomal recessive osteopetrosis, see OPTB1 (259700).
CLINICAL FEATURES
Sly et al. (1972) described 3 sisters, aged 22, 17, and 15 years, born
to normal unrelated North American parents, with a form of osteopetrosis
distinct from both the malignant form (see OPTB1, 259700) and the benign
autosomal dominant form (see OPTA1, 607634). The disorder was manifest
in the first 2 years because of fractures. Other features were short
stature, mental retardation, dental malocclusion, and visual impairment
from optic nerve compression. Mild anemia in infancy improved later and
radiographic features of osteopetrosis improved some at puberty. Serum
acid phosphatase was elevated and electrolyte changes suggested mild
tubular acidosis. Whyte et al. (1980) provided a definitive report of
these sibs. During adolescence basal ganglion calcification developed in
2. Renal tubular acidosis (type I) was diagnosed in each in early
adulthood. Electron microscopy of bone suggested that osteoclasts failed
to form 'ruffled membranes' characteristic of active bone resorbing
cells. Chronic systemic acidosis may have ameliorated the skeletal
manifestations.
Guibaud et al. (1972) described 2 brothers with renal tubular acidosis
and mild osteopetrosis. The unaffected parents, from North Africa, were
cousins. Ohlsson et al. (1980) observed the syndrome, which they
referred to as marble brain disease, in children of 3 Saudi families.
They had striking facial similarities and cerebral calcifications.
Bourke et al. (1981) observed this syndrome in 2 Kuwaiti Bedouin sibs.
One sib showed basal ganglion calcification and mental subnormality. The
major clinical manifestation in both was periodic hypokalemic paresis.
Consanguinity was present in 9 of 12 pedigrees reported by Sly et al.
(1985). More than half the known cases have been in families from
Kuwait, Saudi Arabia, and North Africa. Ohlsson et al. (1986) described
the findings in 4 new Saudi Arabian cases from 2 families, including the
first description in a neonate. They reviewed the 17 previously reported
cases. Cochat et al. (1987) added a case and reviewed the findings in 30
reported patients. Al Rajeh et al. (1988) described 2 affected sisters
in a Saudi Arabian family.
Strisciuglio et al. (1990) described 3 affected Italian sibs, the
offspring of first cousins once removed. They had osteopetrosis with
fractures and severe mental retardation. Whereas most previous patients
had a mixed (proximal and distal) renal tubular acidosis, these patients
had only proximal tubular acidosis.
Aramaki et al. (1993) reported in detail the findings in 3 unrelated
Japanese patients with CA II deficiency. Two of the 3 were born of
first-cousin parents. All exhibited poor activity and poor appetite in
the neonatal period and then developed psychomotor retardation. Two of
them were diagnosed as having osteopetrosis at 10 months and 36 years of
age, respectively, and the third as having osteomalacia at 28 years of
age. All 3 had recurrent episodes of muscle weakness. Their parents
exhibited approximately 50% normal levels of CA II activity in protein.
The development of osteomalacia was considered to be related to the
renal tubular acidosis.
PATHOGENESIS
Sly et al. (1983) were prompted to examine carbonic anhydrase (CA) in
this disorder because sulfonamide inhibitors of CA can produce renal
tubular acidosis and block the parathormone-induced release of calcium
from bone. Although the relationship of CA deficiency to brain
calcification was unclear, it was known that one CA, CA II, is present
in brain and that CA inhibitors reduce CSF production and affect
electric activity of the brain. CA II is the one of the 3 CAs that is
expressed in both brain and kidney. Since it also is expressed in the
red cell, Sly et al. (1983) could study CA II in this tissue of their
patients; they found very low levels in affected persons and
intermediate levels in obligatory heterozygotes. The results indicate a
role of CA II in osteoclast function and bone resorption. The RTA in
this disorder is a hybrid of a mild proximal and prominent distal type.
CA II is the only cytosolic isozyme in the kidney. Red cell CA I
(114800) has been found to be normal in distal RTA.
POPULATION GENETICS
Fathallah et al. (1997) traced the origin of this disorder in 24
Tunisian families with CA II deficiency. All were descended from a
common ancestor who emigrated from the Arabic Peninsula to North Africa
in the 10th century.
MOLECULAR GENETICS
Venta et al. (1990, 1991) sequenced the CA2 gene in a patient with
osteopetrosis and renal tubular acidosis from the consanguineous Belgian
family first described by Vainsel et al. (1972) and identified
homozygosity for a missense mutation (H107Y; 611492.0004).
Roth et al. (1992) analyzed the molecular basis of carbonic anhydrase II
deficiency in the American family in which the association of CA2
deficiency with a clinical syndrome was first recognized by Sly et al.
(1972). The 3 affected sisters were found to be compound heterozygotes
for a maternally inherited H107Y mutation (611492.0004) and a paternally
inherited splice site mutation (611492.0005). Roth et al. (1992)
suggested that residual activity of the H107Y mutant enzyme,
demonstrated in expression studies in bacteria, might explain the
absence of mental retardation and relatively mild phenotype in affected
members of this family.
Hu et al. (1992) pointed out that of the 39 reported cases of carbonic
anhydrase deficiency syndrome, 72% were patients from North Africa and
the Middle East countries, most, if not all, of whom were of Arabic
descent. They showed that members of 6 unrelated Arabic kindreds were in
5 instances homozygous and in 1 instance heterozygous for a splice site
mutation in intron 3 of the CA2 gene (611492.0006). Called the 'Arabic
mutation,' it introduces a new Sau3A1 restriction site useful in
PCR-based diagnosis, carrier detection, and prenatal diagnosis. The
presence of mental retardation and relative infrequency of skeletal
fractures distinguish the clinical course of patients with the Arabic
mutation from that of American and Belgian patients with the H107Y
mutation.
In a 23-year-old Japanese woman previously reported by Aramaki et al.
(1993) ('patient 1' of pedigree A) with carbonic anhydrase II
deficiency, osteopetrosis, renal tubular acidosis, symmetrical cerebral
calcification, and mental retardation, Soda et al. (1995) found a Y40X
mutation in exon 2 of the CA2 gene resulting from a TAT-to-TAG
transversion.
Soda et al. (1996) identified the H107Y mutation in 2 unrelated Japanese
patients previously described by Aramaki et al. (1993), both born of
consanguineous parents, who had osteopetrosis and renal tubular acidosis
as well as severe mental retardation. The authors stated that the basis
for the more severe expression of the H107Y mutation, including mental
retardation, in Japanese patients was unclear.
Hu et al. (1997) identified 7 novel mutations in the CA2 gene in
patients with osteopetrosis and mental retardation or developmental
delay. All but 1 pair of Mexican sibs had renal tubular acidosis also.
Borthwick et al. (2003) described 2 consanguineous Turkish kindreds with
distal RTA and osteopetrosis. In affected members of 1 kindred, the
authors identified homozygosity for a frameshift mutation in the CA2
gene (611492.0008). The authors excluded defects in CA2 in the other
kindred, in which the proband had RTA and osteopetrosis but his sister
manifested only RTA with sensorineural hearing loss and never developed
osteopetrosis. In this kindred, Borthwick et al. (2003) found that the
osteopetrosis (259700) was the result of a homozygous deletion in the
TCIRG1 gene (604592.0007), whereas the distal RTA with hearing loss
(267300) was the result of a homozygous mutation in the ATP6V1B1 gene
(192132.0005). Borthwick et al. (2003) concluded that coinheritance of
these 2 rare recessive disorders created a phenocopy of CA2A deficiency
in this kindred, and commented that this case illustrates the importance
of clinical characterization of all affected members of a kindred.
*FIELD* SA
Sly (1989); Sundaram et al. (1986)
*FIELD* RF
1. Al Rajeh, S.; El Mouzan, M. I.; Ahlberg, A.; Ozaksoy, D.: The
syndrome of osteopetrosis, renal acidosis and cerebral calcification
in two sisters. Neuropediatrics 19: 162-165, 1988.
2. Aramaki, S.; Yoshida, I.; Yoshino, M.; Kondo, M.; Sato, Y.; Noda,
K.; Jo, R.; Okue, A.; Sai, N.; Yamashita, F.: Carbonic anhydrase
II deficiency in three unrelated Japanese patients. J. Inherit. Metab.
Dis. 16: 982-990, 1993.
3. Borthwick, K. J.; Kandemir, N.; Topaloglu, R.; Kornak, U.; Bakkaloglu,
A.; Yordam, N.; Ozen, S.; Mocan, H.; Shah, G. N.; Sly, W. S.; Karet,
F. E.: A phenocopy of CAII deficiency: a novel genetic explanation
for inherited infantile osteopetrosis with distal renal tubular acidosis. J.
Med. Genet. 40: 115-121, 2003.
4. Bourke, E.; Delaney, V. B.; Mosawi, M.; Reavey, P.; Weston, M.
: Renal tubular acidosis and osteopetrosis in siblings. Nephron 28:
268-272, 1981.
5. Cochat, P.; Loras-Duclaux, I.; Guibaud, P.: Deficit en anhydrase
carbonique II: osteopetrose, acidose renale tubulaire et calcifications
intracraniennes. Revue de la literature a'partir de trois observation. Pediatrie 42:
121-128, 1987.
6. Fathallah, D. M.; Bejaoui, M.; Lepaslier, D.; Chater, K.; Sly,
W. S.; Dellagi, K.: Carbonic anhydrase II (CA II) deficiency in Maghrebian
patients: evidence for founder effect and genomic recombination at
the CA II locus. Hum. Genet. 99: 634-637, 1997.
7. Guibaud, P.; Larbre, F.; Freycon, M. T.; Genoud, J.: Osteopetrose
et acidose renale tubulaire. Deux cas de cette association dans une
fratrie. Arch. Franc. Pediat. 29: 269-286, 1972.
8. Hu, P. Y.; Lim, E. J.; Ciccolella, J.; Strisciuglio, P.; Sly, W.
S.: Seven novel mutations in carbonic acid anhydrase II deficiency
syndrome identified by SSCP and direct sequencing analysis. Hum.
Mutat. 9: 383-387, 1997.
9. Hu, P. Y.; Roth, D. E.; Skaggs, L. A.; Venta, P. J.; Tashian, R.
E.; Guibaud, P.; Sly, W. S.: A splice junction mutation in intron
2 of the carbonic anhydrase II gene of osteopetrosis patients from
Arabic countries. Hum. Mutat. 1: 288-292, 1992.
10. Ohlsson, A.; Cumming, W. A.; Paul, A.; Sly, W. S.: Carbonic anhydrase
II deficiency syndrome: recessive osteopetrosis with renal tubular
acidosis and cerebral calcification. Pediatrics 77: 371-381, 1986.
11. Ohlsson, A.; Stark, G.; Sakati, N.: Marble brain disease: recessive
osteopetrosis, renal tubular acidosis and cerebral calcification in
three Saudi Arabian families. Dev. Med. Child Neurol. 22: 72-84,
1980.
12. Roth, D. E.; Venta, P. J.; Tashian, R. E.; Sly, W. S.: Molecular
basis of human carbonic anhydrase II deficiency. Proc. Nat. Acad.
Sci. 89: 1804-1808, 1992.
13. Sly, W. S.: The carbonic anhydrase II deficiency syndrome: osteopetrosis
with renal tubular acidosis and cerebral calcification.In: Scriver,
C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D.: The Metabolic Basis
of Inherited Disease. New York: McGraw-Hill (pub.) (6th ed.)
II: 1989. Pp. 2857-2866.
14. Sly, W. S.; Hewett-Emmett, D.; Whyte, M. P.; Yu, Y.-S. L.; Tashian,
R. E.: Carbonic anhydrase II deficiency identified as the primary
defect in the autosomal recessive syndrome of osteopetrosis with renal
tubular acidosis and cerebral calcification. Proc. Nat. Acad. Sci. 80:
2752-2756, 1983.
15. Sly, W. S.; Lang, R.; Avioli, L.; Haddad, J.; Lubowitz, H.; McAlister,
W.: Recessive osteopetrosis: new clinical phenotype. (Abstract) Am.
J. Hum. Genet. 24: 34A, 1972.
16. Sly, W. S.; Whyte, M. P.; Sundaram, V.; Tashian, R. E.; Hewett-Emmett,
D.; Guibaud, P.; Vainsel, M.; Baluarte, H. J.; Gruskin, A.; Al-Mosawi,
M.; Sakati, N.; Ohlsson, A.: Carbonic anhydrase II deficiency in
12 families with the autosomal recessive syndrome of osteopetrosis
with renal tubular acidosis and cerebral calcification. New Eng.
J. Med. 313: 139-145, 1985.
17. Soda, H.; Yukizane, S.; Yoshida, I.; Aramaki, S.; Kato, H.: Carbonic
anhydrase II deficiency in a Japanese patient produced by a nonsense
mutation (TAT-to-TAG) at tyr-40 in exon 2, (Y40X). Hum. Mutat. 5:
348-350, 1995.
18. Soda, H.; Yukizane, S.; Yoshida, I.; Koga, Y.; Aramaki, S.; Kato,
H.: A point mutation in exon 3 (his107-to-tyr) in two unrelated Japanese
patients with carbonic anhydrase II deficiency with central nervous
system involvement. Hum. Genet. 97: 435-437, 1996.
19. Strisciuglio, P.; Sartorio, R.; Pecoraro, C.; Lotito, F.; Sly,
W. S.: Variable clinical presentation of carbonic anhydrase deficiency:
evidence for heterogeneity? Europ. J. Pediat. 149: 337-340, 1990.
20. Sundaram, V.; Rumbolo, P.; Grubb, J.; Strisciuglio, P.; Sly, W.
S.: Carbonic anhydrase II deficiency: diagnosis and carrier detection
using differential enzyme inhibition and inactivation. Am. J. Hum.
Genet. 38: 125-136, 1986.
21. Vainsel, M.; Fondu, P.; Cadranel, S.; Rocmans, C.; Gepts, W.:
Osteopetrosis associated with proximal and distal tubular acidosis. Acta
Paediat. Scand. 61: 429-434, 1972.
22. Venta, P. J.; Welty, R. J.; Johnson, T. H.; Tashian, R. E.: Human
carbonic anhydrase II deficiency syndrome in a Belgium family appears
to be caused by a destabilizing amino acid substitution (107his-to-tyr).
(Abstract) Am. J. Hum. Genet. 47 (suppl.): A168, 1990.
23. Venta, P. J.; Welty, R. J.; Johnson, T. M.; Sly, W. S.; Tashian,
R. E.: Carbonic anhydrase II deficiency syndrome in a Belgian family
is caused by a point mutation at an invariant histidine residue (107his-to-tyr):
complete structure of the normal human CA II gene. Am. J. Hum. Genet. 49:
1082-1090, 1991.
24. Whyte, M. P.; Murphy, W. A.; Fallon, M. D.; Sly, W. S.; Teitelbaum,
S. L.; McAlister, W. H.; Avioli, L. V.: Osteopetrosis, renal tubular
acidosis and basal ganglia calcification in three sisters. Am. J.
Med. 69: 64-74, 1980.
*FIELD* CS
Growth:
Short stature
GI:
Hepatosplenomegaly
Skel:
Osteosclerosis
HEENT:
Cranial hyperostosis;
Dental malocclusion;
Visual impairment from optic nerve compression
Limbs:
Diaphyseal sclerosis
Neuro:
Basal ganglion calcification;
Normal intelligence or mental retardation
Heme:
Anemia;
Extramedullary hematopoiesis
Misc:
Onset in first 2 years with fractures
Lab:
Renal tubular acidosis, type I;
Elevated serum acid phosphatase;
Osteoclasts fail to form 'ruffled membranes' characteristic of active
bone resorbing cells;
Periodic hypokalemic paresis;
Carbonic anhydrase II defect
Inheritance:
Autosomal recessive
*FIELD* CN
Marla J. F. O'Neill - reorganized: 10/3/2007
Marla J. F. O'Neill - updated: 10/3/2007
Marla J. F. O'Neill - updated: 1/5/2005
Victor A. McKusick - updated: 4/16/1998
Ada Hamosh - updated: 7/10/1997
Victor A. McKusick - updated: 6/18/1997
Moyra Smith - updated: 3/13/1996
Orest Hurko - updated: 8/15/1995
*FIELD* CD
Victor A. McKusick: 6/4/1986
*FIELD* ED
alopez: 02/19/2013
carol: 10/10/2007
carol: 10/3/2007
terry: 4/4/2005
carol: 1/5/2005
carol: 3/17/2004
carol: 2/2/2004
carol: 3/1/2000
carol: 9/29/1999
carol: 9/28/1998
dkim: 9/10/1998
dholmes: 5/11/1998
carol: 5/2/1998
terry: 4/16/1998
alopez: 8/26/1997
alopez: 7/10/1997
jenny: 6/23/1997
mark: 6/18/1997
terry: 4/15/1996
mark: 3/13/1996
terry: 3/13/1996
mark: 3/13/1996
mark: 7/6/1995
pfoster: 8/17/1994
terry: 7/18/1994
jason: 7/12/1994
MIM
611492
*RECORD*
*FIELD* NO
611492
*FIELD* TI
*611492 CARBONIC ANHYDRASE II; CA2
;;CA II;;
CARBONIC ANHYDRASE B;;
CARBONIC ANHYDRASE C, FORMERLY
read more*FIELD* TX
DESCRIPTION
Carbonic anhydrases (CAs) are a family of zinc metalloenzymes. For
background information on the CA family, see 114800.
GENE STRUCTURE
Using Southern blot analysis and restriction endonucleases, Venta et al.
(1991) determined that the CA2 gene consists of 7 exons.
MAPPING
Using a mouse CA II cDNA hybridization probe with a panel of mouse-human
cell hybrids, Venta et al. (1983) assigned the CA2 gene to human
chromosome 8. By in situ hybridization, Nakai et al. (1987) localized
CA2 to 8q22. By pulsed field gradient gel electrophoresis, Venta et al.
(1987) showed that the CA1 (114800) and CA2 genes are separated by at
least 27 kb, with CA1 located upstream to CA2.
GENE FUNCTION
Carbonic anhydrase II is expressed at high levels in osteoclasts during
bone resorption. Laitala and Vaananen (1994) demonstrated in 2 in vitro
culture systems that antisense RNA and DNA blocked expression of CA II
and led to decreased bone resorption. In the choroid plexus, carbonic
anhydrase II supports the transport of bicarbonate ions, sodium ions,
and water from the blood to the cerebrospinal fluid.
MOLECULAR GENETICS
Electrophoretic variants of carbonic anhydrase II (formerly called
carbonic anhydrase C and later carbonic anhydrase B) were described by
Moore et al. (1971) in American blacks. Several variants of carbonic
anhydrase II have been characterized in humans. Tashian et al. (1968)
found CA II variants in monkeys.
Data on gene frequencies of allelic variants were tabulated by
Roychoudhury and Nei (1988).
Venta et al. (1990, 1991) sequenced the CA2 gene in a patient from a
consanguineous Belgian family with osteopetrosis and renal tubular
acidosis (OPTB3; 259730), first described by Vainsel et al. (1972), and
identified homozygosity for a missense mutation (H107Y; 611492.0004).
Roth et al. (1992) analyzed the CA2 gene in the 3 affected sisters of
the American family in which the association of CA2 deficiency with a
clinical syndrome was first recognized by Sly et al. (1972) and
identified compound heterozygosity for a maternally inherited H107Y
mutation and a paternally inherited splice site mutation (611492.0005).
Roth et al. (1992) suggested that residual activity of the H107Y mutant
enzyme, demonstrated in expression studies in bacteria, might explain
the absence of mental retardation and relatively mild phenotype in
affected members of this family.
Hu et al. (1992) noted that of the 39 reported cases of carbonic
anhydrase deficiency syndrome, 72% were patients from North Africa and
the Middle East countries, most, if not all, of whom were of Arabic
descent. They found that members of 6 unrelated Arabic kindreds were in
5 instances homozygous and in 1 instance heterozygous for a novel splice
site mutation (611492.0006) which they designated the 'Arabic mutation.'
In a 23-year-old Japanese woman previously reported by Aramaki et al.
(1993) ('patient 1' of pedigree A) with carbonic anhydrase II deficiency
and osteopetrosis, renal tubular acidosis, symmetrical cerebral
calcification, and mental retardation, Soda et al. (1995) found a
nonsense mutation in the CA2 gene (Y40X; 611492.0007).
Soda et al. (1996) identified the H107Y mutation in 2 unrelated Japanese
patients previously described by Aramaki et al. (1993), both born of
consanguineous parents, who had osteopetrosis and renal tubular acidosis
as well as severe mental retardation. The authors stated that the basis
for the more severe expression of the H107Y mutation, including mental
retardation, in Japanese patients was unclear.
ANIMAL MODEL
Lewis et al. (1988) used induced mutagenesis to produce a strain of CA
II-null mice that showed growth retardation and renal tubular acidosis.
A point mutation was found at gln154 that led to premature termination
of translation. Brechue et al. (1991) found that the renal defects in
these CA II-deficient mice included the inability to acidify urine after
challenge with an acid load.
Lai et al. (1998) used C57BL/6J Car-2 CA II-null mice for a trial of
gene therapy. They reported that retrograde injection of cationic
liposome complexed with a CA II chimeric gene, using a cytomegalovirus
(CMV) promoter/enhancer as an expression cassette to drive human CA2
cDNA, into the renal pelvis of CA II-deficient mice resulted in
expression of CA II in the kidney. The levels of both the CA2 gene and
its corresponding mRNA was highest by day 3 after treatment, diminishing
thereafter, but remaining detectable by 1 month. After gene therapy, the
deficient mice restored the ability to acidify urine after oral
administration of ammonium chloride. The ability to acidify urine was
maintained at 3 weeks after gene therapy and was eventually lost by 6
weeks.
Cammer et al. (1995) studied mutant mice deficient in carbonic anhydrase
II (Car-2n) and found that they have normal compact myelin. However, in
double mutant mice for both Car2 and partial deficiency of myelin basic
protein, they found abnormal myelin in the double mutants, but not in
the single mutants. This suggested a role of carbonic anhydrase II in
the compaction of myelin membranes.
*FIELD* AV
.0001
CARBONIC ANHYDRASE II VARIANT
CA2, ASN252ASP
Lin and Deutsch (1972) found a variant form with substitution of
aspartic acid for asparagine at residue 252, presumed to represent a
substitution of G for A at nucleotide 819.
.0002
CARBONIC ANHYDRASE II VARIANT
CA2, LYS17GLU
Jones et al. (1982) described a variant with substitution of glutamic
acid for lysine at residue 17, presumed to represent a substitution of G
for A at nucleotide 117.
.0003
CARBONIC ANHYDRASE II VARIANT
CA2, PRO237HIS
Jones and Shaw (1983) described a variant with substitution of histidine
for proline at amino acid 237, presumed to represent a substitution of A
for C at nucleotide 771.
.0004
OSTEOPETROSIS, AUTOSOMAL RECESSIVE 3
CA2, HIS107TYR
In a patient with osteopetrosis and renal tubular acidosis (OPTB3;
259730) from a consanguineous Belgian family first described by Vainsel
et al. (1972), Venta et al. (1990, 1991) identified homozygosity for a
C-T transition in exon 3 of the CA2 gene, resulting in the substitution
of tyrosine for the highly conserved histidine at codon 107 (H107Y).
Roth et al. (1992) analyzed the molecular basis of carbonic anhydrase II
deficiency in the American family in which the association of CA2
deficiency with a clinical syndrome (OPTB3) was first recognized by Sly
et al. (1972). The 3 affected sisters were found to be compound
heterozygotes for mutations in the CA2 gene: a maternally inherited
H107Y mutation on one allele, and a paternally inherited G-C
transversion in the A-G splice acceptor dinucleotide at the 3-prime end
of intron 5 (611492.0005) on the other allele. Roth et al. (1992)
suggested that residual activity of the H107Y mutant enzyme,
demonstrated in expression studies in bacteria, might explain the
absence of mental retardation and relatively mild phenotype in affected
members of this family.
Soda et al. (1996) identified the H107Y mutation in 2 unrelated Japanese
patients previously described by Aramaki et al. (1993), both born of
consanguineous parents, who had osteopetrosis and renal tubular acidosis
as well as severe mental retardation. Mental retardation was not seen in
the Belgian patient reported by Venta et al. (1991) or the American
sisters described by Roth et al. (1992). Soda et al. (1996) suggested
that the small amount of residual CA II activity with the H107Y mutation
may not always allow patients to escape mental retardation.
.0005
OSTEOPETROSIS, AUTOSOMAL RECESSIVE 3
CA2, IVS5, G-C, -1
See 611492.0004 and Roth et al. (1992).
.0006
OSTEOPETROSIS, AUTOSOMAL RECESSIVE 3
CA2, IVS2, G-A, +1
Hu et al. (1992) pointed out that of the 39 reported cases of carbonic
anhydrase deficiency syndrome (259730), 72% were patients from North
Africa and the Middle East countries, most, if not all, of whom were of
Arabic descent. They showed that members of 6 unrelated Arabic kindreds
were in 5 instances homozygous and in 1 instance heterozygous for a
novel splice junction at the 5-prime end of intron 2. Called the 'Arabic
mutation,' it introduces a new Sau3A1 restriction site useful in
PCR-based diagnosis, carrier detection, and prenatal diagnosis. The
presence of mental retardation and relative infrequency of skeletal
fractures distinguish the clinical course of patients with the Arabic
mutation from that of American and Belgian patients with the H107Y
mutation (611492.0004).
.0007
OSTEOPETROSIS, AUTOSOMAL RECESSIVE 3
CA2, TYR40TER
In a 23-year-old Japanese woman previously reported by Aramaki et al.
(1993) ('patient 1' of pedigree A) with carbonic anhydrase II deficiency
and osteopetrosis, renal tubular acidosis, symmetrical cerebral
calcification, and mental retardation (259730), Soda et al. (1995) found
a Y40X mutation in exon 2 of the CA2 gene resulting from a TAT-to-TAG
transversion.
.0008
OSTEOPETROSIS, AUTOSOMAL RECESSIVE 3
CA2, 1-BP DEL, 207C
In 2 sibs of a consanguineous Turkish family with osteopetrosis and
renal tubular acidosis (259730), Borthwick et al. (2003) identified
homozygosity for deletion of a single cytosine in codon 207, leading to
a premature termination codon 15 amino acids downstream. Both unaffected
parents were heterozygous for the mutation and had only intermediate
activity of CA2.
*FIELD* SA
Ghosh et al. (1979); Lin and Deutsch (1974); Montgomery et al. (1987);
Ueda et al. (1977)
*FIELD* RF
1. Aramaki, S.; Yoshida, I.; Yoshino, M.; Kondo, M.; Sato, Y.; Noda,
K.; Jo, R.; Okue, A.; Sai, N.; Yamashita, F.: Carbonic anhydrase
II deficiency in three unrelated Japanese patients. J. Inherit. Metab.
Dis. 16: 982-990, 1993.
2. Borthwick, K. J.; Kandemir, N.; Topaloglu, R.; Kornak, U.; Bakkaloglu,
A.; Yordam, N.; Ozen, S.; Mocan, H.; Shah, G. N.; Sly, W. S.; Karet,
F. E.: A phenocopy of CAII deficiency: a novel genetic explanation
for inherited infantile osteopetrosis with distal renal tubular acidosis. J.
Med. Genet. 40: 115-121, 2003.
3. Brechue, W. F.; Kinne-Saffran, E.; Kinne, R. K. H.; Maren, T. H.
: Localization and activity of renal carbonic anhydrase (CA) in CA-II
deficient mice. Biochim. Biophys. Acta 1066: 201-207, 1991.
4. Cammer, W.; Zhang, H.; Tansey, F. A.: Effects of carbonic anhydrase
II (CAII) deficiency on CNS structure and function in the myelin-deficient
CAII-deficient double mutant mouse. J. Neurosci. Res. 40: 451-457,
1995.
5. Ghosh, A. K.; Dey, B.; Bharati, P.; Blake, N. M.: A new variant
of carbonic anhydrase in West Bengal. Acta Anthropogenetica 3: 71-74,
1979.
6. Hu, P. Y.; Roth, D. E.; Skaggs, L. A.; Venta, P. J.; Tashian, R.
E.; Guibaud, P.; Sly, W. S.: A splice junction mutation in intron
2 of the carbonic anhydrase II gene of osteopetrosis patients from
Arabic countries. Hum. Mutat. 1: 288-292, 1992.
7. Jones, G. L.; Shaw, D. C.: A chemical and enzymological comparison
of the common major human erythrocyte carbonic anhydrase II, its minor
component, and a new genetic variant, CA II(Melbourne)(237 pro-to-his). Hum.
Genet. 63: 392-399, 1983.
8. Jones, G. L.; Sofro, A. S. M.; Shaw, D. C.: Chemical and enzymological
characterization of an Indonesian variant of human erythrocyte carbonic
anhydrase II, CAII(Jogjakarta) (17 lys-to-glu). Biochem. Genet. 20:
979-1000, 1982.
9. Lai, L.-W.; Chan, D. M.; Erickson, R. P.; Hsu, S. J.; Lien, Y.-H.
H.: Correction of renal tubular acidosis in carbonic anhydrase II-deficient
mice with gene therapy. J. Clin. Invest. 101: 1320-1325, 1998.
10. Laitala, T.; Vaananen, H. K.: Inhibition of bone resorption in
vitro by antisense RNA and DNA molecules targeted against carbonic
anhydrase II or two subunits of vacuolar H(+)-ATPase. J. Clin. Invest. 93:
2311-2318, 1994.
11. Lewis, S. E.; Erickson, R. P.; Barnett, L. B.; Venta, P. J.; Tashian,
R. E.: N-ethyl-N-nitrosourea-induced null mutation at the mouse Car-2
locus: an animal model for human carbonic anhydrase II deficiency
syndrome. Proc. Nat. Acad. Sci. 85: 1962-1966, 1988.
12. Lin, K.-T. D.; Deutsch, H. F.: Human carbonic anhydrase. VIII.
Isolation and characterization of a polymorphic form of a C-type isozyme. J.
Biol. Chem. 247: 3761-3766, 1972.
13. Lin, K.-T. D.; Deutsch, H. F.: Human carbonic anhydrase. XII.
The complete primary structure of the C isozyme. J. Biol. Chem. 249:
2329-2337, 1974.
14. Montgomery, J. C.; Venta, P. J.; Tashian, R. E.; Hewett-Emmett,
D.: Nucleotide sequence of human liver carbonic anhydrase II cDNA. Nucleic
Acids Res. 15: 4687, 1987.
15. Moore, M. J.; Funakoshi, S.; Deutsch, H. F.: Human carbonic anhydrase.
VII. A new C type isozyme in erythrocytes of American Negroes. Biochem.
Genet. 5: 497-504, 1971.
16. Nakai, H.; Byers, M. G.; Venta, P. J.; Tashian, R. E.; Shows,
T. B.: The gene for human carbonic anhydrase II (CA2) is located
at chromosome 8q22. Cytogenet. Cell Genet. 44: 234-235, 1987.
17. Roth, D. E.; Venta, P. J.; Tashian, R. E.; Sly, W. S.: Molecular
basis of human carbonic anhydrase II deficiency. Proc. Nat. Acad.
Sci. 89: 1804-1808, 1992.
18. Roychoudhury, A. K.; Nei, M.: Human Polymorphic Genes: World
Distribution. New York: Oxford Univ. Press , 1988.
19. Sly, W. S.; Lang, R.; Avioli, L.; Haddad, J.; Lubowitz, H.; McAlister,
W.: Recessive osteopetrosis: new clinical phenotype. (Abstract) Am.
J. Hum. Genet. 24: 34A, 1972.
20. Soda, H.; Yukizane, S.; Yoshida, I.; Aramaki, S.; Kato, H.: Carbonic
anhydrase II deficiency in a Japanese patient produced by a nonsense
mutation (TAT-to-TAG) at tyr-40 in exon 2, (Y40X). Hum. Mutat. 5:
348-350, 1995.
21. Soda, H.; Yukizane, S.; Yoshida, I.; Koga, Y.; Aramaki, S.; Kato,
H.: A point mutation in exon 3 (his107-to-tyr) in two unrelated Japanese
patients with carbonic anhydrase II deficiency with central nervous
system involvement. Hum. Genet. 97: 435-437, 1996.
22. Tashian, R. E.; Schreffler, D. C.; Shows, T. B.: Genetic and
phylogenetic variation in the different molecular forms of mammalian
erythrocyte carbonic anhydrases. Ann. N.Y. Acad. Sci. 151: 64-77,
1968.
23. Ueda, N.; Satoh, C.; Tanis, R. J.; Ferrell, R. E.; Koshimoto,
S.; Neel, J. V.; Hamilton, H. B.; Baba, K.: The frequency in Japanese
of genetic variants of 22 proteins. II. Carbonic anhydrase I and II,
lactate dehydrogenase, malate dehydrogenase, nucleoside phosphorylase,
triosephosphate isomerase, haemoglobin A and haemoglobin A-2. Ann.
Hum. Genet. 41: 43-52, 1977.
24. Vainsel, M.; Fondu, P.; Cadranel, S.; Rocmans, C.; Gepts, W.:
Osteopetrosis associated with proximal and distal tubular acidosis. Acta
Paediat. Scand. 61: 429-434, 1972.
25. Venta, P. J.; Montgomery, J. C.; Tashian, R. E.: Molecular genetics
of carbonic anhydrase isozymes.In: Rattazzi, M. C.; Scandalios, J.
C.; Whitt, G. S.: Isozymes. Current Topics in Biological and Medical
Research. New York: Alan R. Liss (pub.) 1987.
26. Venta, P. J.; Shows, T. B.; Curtis, P. J.; Tashian, R. E.: Polymorphic
gene for human carbonic anhydrase II: a molecular disease marker located
on chromosome 8. Proc. Nat. Acad. Sci. 80: 4437-4440, 1983.
27. Venta, P. J.; Welty, R. J.; Johnson, T. H.; Tashian, R. E.: Human
carbonic anhydrase II deficiency syndrome in a Belgium family appears
to be caused by a destabilizing amino acid substitution (107his-to-tyr).
(Abstract) Am. J. Hum. Genet. 47 (suppl.): A168, 1990.
28. Venta, P. J.; Welty, R. J.; Johnson, T. M.; Sly, W. S.; Tashian,
R. E.: Carbonic anhydrase II deficiency syndrome in a Belgian family
is caused by a point mutation at an invariant histidine residue (107his-to-tyr):
complete structure of the normal human CA II gene. Am. J. Hum. Genet. 49:
1082-1090, 1991.
*FIELD* CD
Marla J. F. O'Neill: 10/3/2007
*FIELD* ED
carol: 12/01/2009
carol: 10/11/2007
carol: 10/3/2007
*RECORD*
*FIELD* NO
611492
*FIELD* TI
*611492 CARBONIC ANHYDRASE II; CA2
;;CA II;;
CARBONIC ANHYDRASE B;;
CARBONIC ANHYDRASE C, FORMERLY
read more*FIELD* TX
DESCRIPTION
Carbonic anhydrases (CAs) are a family of zinc metalloenzymes. For
background information on the CA family, see 114800.
GENE STRUCTURE
Using Southern blot analysis and restriction endonucleases, Venta et al.
(1991) determined that the CA2 gene consists of 7 exons.
MAPPING
Using a mouse CA II cDNA hybridization probe with a panel of mouse-human
cell hybrids, Venta et al. (1983) assigned the CA2 gene to human
chromosome 8. By in situ hybridization, Nakai et al. (1987) localized
CA2 to 8q22. By pulsed field gradient gel electrophoresis, Venta et al.
(1987) showed that the CA1 (114800) and CA2 genes are separated by at
least 27 kb, with CA1 located upstream to CA2.
GENE FUNCTION
Carbonic anhydrase II is expressed at high levels in osteoclasts during
bone resorption. Laitala and Vaananen (1994) demonstrated in 2 in vitro
culture systems that antisense RNA and DNA blocked expression of CA II
and led to decreased bone resorption. In the choroid plexus, carbonic
anhydrase II supports the transport of bicarbonate ions, sodium ions,
and water from the blood to the cerebrospinal fluid.
MOLECULAR GENETICS
Electrophoretic variants of carbonic anhydrase II (formerly called
carbonic anhydrase C and later carbonic anhydrase B) were described by
Moore et al. (1971) in American blacks. Several variants of carbonic
anhydrase II have been characterized in humans. Tashian et al. (1968)
found CA II variants in monkeys.
Data on gene frequencies of allelic variants were tabulated by
Roychoudhury and Nei (1988).
Venta et al. (1990, 1991) sequenced the CA2 gene in a patient from a
consanguineous Belgian family with osteopetrosis and renal tubular
acidosis (OPTB3; 259730), first described by Vainsel et al. (1972), and
identified homozygosity for a missense mutation (H107Y; 611492.0004).
Roth et al. (1992) analyzed the CA2 gene in the 3 affected sisters of
the American family in which the association of CA2 deficiency with a
clinical syndrome was first recognized by Sly et al. (1972) and
identified compound heterozygosity for a maternally inherited H107Y
mutation and a paternally inherited splice site mutation (611492.0005).
Roth et al. (1992) suggested that residual activity of the H107Y mutant
enzyme, demonstrated in expression studies in bacteria, might explain
the absence of mental retardation and relatively mild phenotype in
affected members of this family.
Hu et al. (1992) noted that of the 39 reported cases of carbonic
anhydrase deficiency syndrome, 72% were patients from North Africa and
the Middle East countries, most, if not all, of whom were of Arabic
descent. They found that members of 6 unrelated Arabic kindreds were in
5 instances homozygous and in 1 instance heterozygous for a novel splice
site mutation (611492.0006) which they designated the 'Arabic mutation.'
In a 23-year-old Japanese woman previously reported by Aramaki et al.
(1993) ('patient 1' of pedigree A) with carbonic anhydrase II deficiency
and osteopetrosis, renal tubular acidosis, symmetrical cerebral
calcification, and mental retardation, Soda et al. (1995) found a
nonsense mutation in the CA2 gene (Y40X; 611492.0007).
Soda et al. (1996) identified the H107Y mutation in 2 unrelated Japanese
patients previously described by Aramaki et al. (1993), both born of
consanguineous parents, who had osteopetrosis and renal tubular acidosis
as well as severe mental retardation. The authors stated that the basis
for the more severe expression of the H107Y mutation, including mental
retardation, in Japanese patients was unclear.
ANIMAL MODEL
Lewis et al. (1988) used induced mutagenesis to produce a strain of CA
II-null mice that showed growth retardation and renal tubular acidosis.
A point mutation was found at gln154 that led to premature termination
of translation. Brechue et al. (1991) found that the renal defects in
these CA II-deficient mice included the inability to acidify urine after
challenge with an acid load.
Lai et al. (1998) used C57BL/6J Car-2 CA II-null mice for a trial of
gene therapy. They reported that retrograde injection of cationic
liposome complexed with a CA II chimeric gene, using a cytomegalovirus
(CMV) promoter/enhancer as an expression cassette to drive human CA2
cDNA, into the renal pelvis of CA II-deficient mice resulted in
expression of CA II in the kidney. The levels of both the CA2 gene and
its corresponding mRNA was highest by day 3 after treatment, diminishing
thereafter, but remaining detectable by 1 month. After gene therapy, the
deficient mice restored the ability to acidify urine after oral
administration of ammonium chloride. The ability to acidify urine was
maintained at 3 weeks after gene therapy and was eventually lost by 6
weeks.
Cammer et al. (1995) studied mutant mice deficient in carbonic anhydrase
II (Car-2n) and found that they have normal compact myelin. However, in
double mutant mice for both Car2 and partial deficiency of myelin basic
protein, they found abnormal myelin in the double mutants, but not in
the single mutants. This suggested a role of carbonic anhydrase II in
the compaction of myelin membranes.
*FIELD* AV
.0001
CARBONIC ANHYDRASE II VARIANT
CA2, ASN252ASP
Lin and Deutsch (1972) found a variant form with substitution of
aspartic acid for asparagine at residue 252, presumed to represent a
substitution of G for A at nucleotide 819.
.0002
CARBONIC ANHYDRASE II VARIANT
CA2, LYS17GLU
Jones et al. (1982) described a variant with substitution of glutamic
acid for lysine at residue 17, presumed to represent a substitution of G
for A at nucleotide 117.
.0003
CARBONIC ANHYDRASE II VARIANT
CA2, PRO237HIS
Jones and Shaw (1983) described a variant with substitution of histidine
for proline at amino acid 237, presumed to represent a substitution of A
for C at nucleotide 771.
.0004
OSTEOPETROSIS, AUTOSOMAL RECESSIVE 3
CA2, HIS107TYR
In a patient with osteopetrosis and renal tubular acidosis (OPTB3;
259730) from a consanguineous Belgian family first described by Vainsel
et al. (1972), Venta et al. (1990, 1991) identified homozygosity for a
C-T transition in exon 3 of the CA2 gene, resulting in the substitution
of tyrosine for the highly conserved histidine at codon 107 (H107Y).
Roth et al. (1992) analyzed the molecular basis of carbonic anhydrase II
deficiency in the American family in which the association of CA2
deficiency with a clinical syndrome (OPTB3) was first recognized by Sly
et al. (1972). The 3 affected sisters were found to be compound
heterozygotes for mutations in the CA2 gene: a maternally inherited
H107Y mutation on one allele, and a paternally inherited G-C
transversion in the A-G splice acceptor dinucleotide at the 3-prime end
of intron 5 (611492.0005) on the other allele. Roth et al. (1992)
suggested that residual activity of the H107Y mutant enzyme,
demonstrated in expression studies in bacteria, might explain the
absence of mental retardation and relatively mild phenotype in affected
members of this family.
Soda et al. (1996) identified the H107Y mutation in 2 unrelated Japanese
patients previously described by Aramaki et al. (1993), both born of
consanguineous parents, who had osteopetrosis and renal tubular acidosis
as well as severe mental retardation. Mental retardation was not seen in
the Belgian patient reported by Venta et al. (1991) or the American
sisters described by Roth et al. (1992). Soda et al. (1996) suggested
that the small amount of residual CA II activity with the H107Y mutation
may not always allow patients to escape mental retardation.
.0005
OSTEOPETROSIS, AUTOSOMAL RECESSIVE 3
CA2, IVS5, G-C, -1
See 611492.0004 and Roth et al. (1992).
.0006
OSTEOPETROSIS, AUTOSOMAL RECESSIVE 3
CA2, IVS2, G-A, +1
Hu et al. (1992) pointed out that of the 39 reported cases of carbonic
anhydrase deficiency syndrome (259730), 72% were patients from North
Africa and the Middle East countries, most, if not all, of whom were of
Arabic descent. They showed that members of 6 unrelated Arabic kindreds
were in 5 instances homozygous and in 1 instance heterozygous for a
novel splice junction at the 5-prime end of intron 2. Called the 'Arabic
mutation,' it introduces a new Sau3A1 restriction site useful in
PCR-based diagnosis, carrier detection, and prenatal diagnosis. The
presence of mental retardation and relative infrequency of skeletal
fractures distinguish the clinical course of patients with the Arabic
mutation from that of American and Belgian patients with the H107Y
mutation (611492.0004).
.0007
OSTEOPETROSIS, AUTOSOMAL RECESSIVE 3
CA2, TYR40TER
In a 23-year-old Japanese woman previously reported by Aramaki et al.
(1993) ('patient 1' of pedigree A) with carbonic anhydrase II deficiency
and osteopetrosis, renal tubular acidosis, symmetrical cerebral
calcification, and mental retardation (259730), Soda et al. (1995) found
a Y40X mutation in exon 2 of the CA2 gene resulting from a TAT-to-TAG
transversion.
.0008
OSTEOPETROSIS, AUTOSOMAL RECESSIVE 3
CA2, 1-BP DEL, 207C
In 2 sibs of a consanguineous Turkish family with osteopetrosis and
renal tubular acidosis (259730), Borthwick et al. (2003) identified
homozygosity for deletion of a single cytosine in codon 207, leading to
a premature termination codon 15 amino acids downstream. Both unaffected
parents were heterozygous for the mutation and had only intermediate
activity of CA2.
*FIELD* SA
Ghosh et al. (1979); Lin and Deutsch (1974); Montgomery et al. (1987);
Ueda et al. (1977)
*FIELD* RF
1. Aramaki, S.; Yoshida, I.; Yoshino, M.; Kondo, M.; Sato, Y.; Noda,
K.; Jo, R.; Okue, A.; Sai, N.; Yamashita, F.: Carbonic anhydrase
II deficiency in three unrelated Japanese patients. J. Inherit. Metab.
Dis. 16: 982-990, 1993.
2. Borthwick, K. J.; Kandemir, N.; Topaloglu, R.; Kornak, U.; Bakkaloglu,
A.; Yordam, N.; Ozen, S.; Mocan, H.; Shah, G. N.; Sly, W. S.; Karet,
F. E.: A phenocopy of CAII deficiency: a novel genetic explanation
for inherited infantile osteopetrosis with distal renal tubular acidosis. J.
Med. Genet. 40: 115-121, 2003.
3. Brechue, W. F.; Kinne-Saffran, E.; Kinne, R. K. H.; Maren, T. H.
: Localization and activity of renal carbonic anhydrase (CA) in CA-II
deficient mice. Biochim. Biophys. Acta 1066: 201-207, 1991.
4. Cammer, W.; Zhang, H.; Tansey, F. A.: Effects of carbonic anhydrase
II (CAII) deficiency on CNS structure and function in the myelin-deficient
CAII-deficient double mutant mouse. J. Neurosci. Res. 40: 451-457,
1995.
5. Ghosh, A. K.; Dey, B.; Bharati, P.; Blake, N. M.: A new variant
of carbonic anhydrase in West Bengal. Acta Anthropogenetica 3: 71-74,
1979.
6. Hu, P. Y.; Roth, D. E.; Skaggs, L. A.; Venta, P. J.; Tashian, R.
E.; Guibaud, P.; Sly, W. S.: A splice junction mutation in intron
2 of the carbonic anhydrase II gene of osteopetrosis patients from
Arabic countries. Hum. Mutat. 1: 288-292, 1992.
7. Jones, G. L.; Shaw, D. C.: A chemical and enzymological comparison
of the common major human erythrocyte carbonic anhydrase II, its minor
component, and a new genetic variant, CA II(Melbourne)(237 pro-to-his). Hum.
Genet. 63: 392-399, 1983.
8. Jones, G. L.; Sofro, A. S. M.; Shaw, D. C.: Chemical and enzymological
characterization of an Indonesian variant of human erythrocyte carbonic
anhydrase II, CAII(Jogjakarta) (17 lys-to-glu). Biochem. Genet. 20:
979-1000, 1982.
9. Lai, L.-W.; Chan, D. M.; Erickson, R. P.; Hsu, S. J.; Lien, Y.-H.
H.: Correction of renal tubular acidosis in carbonic anhydrase II-deficient
mice with gene therapy. J. Clin. Invest. 101: 1320-1325, 1998.
10. Laitala, T.; Vaananen, H. K.: Inhibition of bone resorption in
vitro by antisense RNA and DNA molecules targeted against carbonic
anhydrase II or two subunits of vacuolar H(+)-ATPase. J. Clin. Invest. 93:
2311-2318, 1994.
11. Lewis, S. E.; Erickson, R. P.; Barnett, L. B.; Venta, P. J.; Tashian,
R. E.: N-ethyl-N-nitrosourea-induced null mutation at the mouse Car-2
locus: an animal model for human carbonic anhydrase II deficiency
syndrome. Proc. Nat. Acad. Sci. 85: 1962-1966, 1988.
12. Lin, K.-T. D.; Deutsch, H. F.: Human carbonic anhydrase. VIII.
Isolation and characterization of a polymorphic form of a C-type isozyme. J.
Biol. Chem. 247: 3761-3766, 1972.
13. Lin, K.-T. D.; Deutsch, H. F.: Human carbonic anhydrase. XII.
The complete primary structure of the C isozyme. J. Biol. Chem. 249:
2329-2337, 1974.
14. Montgomery, J. C.; Venta, P. J.; Tashian, R. E.; Hewett-Emmett,
D.: Nucleotide sequence of human liver carbonic anhydrase II cDNA. Nucleic
Acids Res. 15: 4687, 1987.
15. Moore, M. J.; Funakoshi, S.; Deutsch, H. F.: Human carbonic anhydrase.
VII. A new C type isozyme in erythrocytes of American Negroes. Biochem.
Genet. 5: 497-504, 1971.
16. Nakai, H.; Byers, M. G.; Venta, P. J.; Tashian, R. E.; Shows,
T. B.: The gene for human carbonic anhydrase II (CA2) is located
at chromosome 8q22. Cytogenet. Cell Genet. 44: 234-235, 1987.
17. Roth, D. E.; Venta, P. J.; Tashian, R. E.; Sly, W. S.: Molecular
basis of human carbonic anhydrase II deficiency. Proc. Nat. Acad.
Sci. 89: 1804-1808, 1992.
18. Roychoudhury, A. K.; Nei, M.: Human Polymorphic Genes: World
Distribution. New York: Oxford Univ. Press , 1988.
19. Sly, W. S.; Lang, R.; Avioli, L.; Haddad, J.; Lubowitz, H.; McAlister,
W.: Recessive osteopetrosis: new clinical phenotype. (Abstract) Am.
J. Hum. Genet. 24: 34A, 1972.
20. Soda, H.; Yukizane, S.; Yoshida, I.; Aramaki, S.; Kato, H.: Carbonic
anhydrase II deficiency in a Japanese patient produced by a nonsense
mutation (TAT-to-TAG) at tyr-40 in exon 2, (Y40X). Hum. Mutat. 5:
348-350, 1995.
21. Soda, H.; Yukizane, S.; Yoshida, I.; Koga, Y.; Aramaki, S.; Kato,
H.: A point mutation in exon 3 (his107-to-tyr) in two unrelated Japanese
patients with carbonic anhydrase II deficiency with central nervous
system involvement. Hum. Genet. 97: 435-437, 1996.
22. Tashian, R. E.; Schreffler, D. C.; Shows, T. B.: Genetic and
phylogenetic variation in the different molecular forms of mammalian
erythrocyte carbonic anhydrases. Ann. N.Y. Acad. Sci. 151: 64-77,
1968.
23. Ueda, N.; Satoh, C.; Tanis, R. J.; Ferrell, R. E.; Koshimoto,
S.; Neel, J. V.; Hamilton, H. B.; Baba, K.: The frequency in Japanese
of genetic variants of 22 proteins. II. Carbonic anhydrase I and II,
lactate dehydrogenase, malate dehydrogenase, nucleoside phosphorylase,
triosephosphate isomerase, haemoglobin A and haemoglobin A-2. Ann.
Hum. Genet. 41: 43-52, 1977.
24. Vainsel, M.; Fondu, P.; Cadranel, S.; Rocmans, C.; Gepts, W.:
Osteopetrosis associated with proximal and distal tubular acidosis. Acta
Paediat. Scand. 61: 429-434, 1972.
25. Venta, P. J.; Montgomery, J. C.; Tashian, R. E.: Molecular genetics
of carbonic anhydrase isozymes.In: Rattazzi, M. C.; Scandalios, J.
C.; Whitt, G. S.: Isozymes. Current Topics in Biological and Medical
Research. New York: Alan R. Liss (pub.) 1987.
26. Venta, P. J.; Shows, T. B.; Curtis, P. J.; Tashian, R. E.: Polymorphic
gene for human carbonic anhydrase II: a molecular disease marker located
on chromosome 8. Proc. Nat. Acad. Sci. 80: 4437-4440, 1983.
27. Venta, P. J.; Welty, R. J.; Johnson, T. H.; Tashian, R. E.: Human
carbonic anhydrase II deficiency syndrome in a Belgium family appears
to be caused by a destabilizing amino acid substitution (107his-to-tyr).
(Abstract) Am. J. Hum. Genet. 47 (suppl.): A168, 1990.
28. Venta, P. J.; Welty, R. J.; Johnson, T. M.; Sly, W. S.; Tashian,
R. E.: Carbonic anhydrase II deficiency syndrome in a Belgian family
is caused by a point mutation at an invariant histidine residue (107his-to-tyr):
complete structure of the normal human CA II gene. Am. J. Hum. Genet. 49:
1082-1090, 1991.
*FIELD* CD
Marla J. F. O'Neill: 10/3/2007
*FIELD* ED
carol: 12/01/2009
carol: 10/11/2007
carol: 10/3/2007