MTCA1_MYCTU
ID MTCA1_MYCTU Reviewed; 163 AA.
AC P9WPJ7; L0T7U0; P64797; Q10612;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 43.
DE RecName: Full=Beta-carbonic anhydrase 1 {ECO:0000303|PubMed:19317447};
DE Short=Beta-CA 1 {ECO:0000303|PubMed:19317447};
DE EC=4.2.1.1 {ECO:0000269|PubMed:19317447, ECO:0000269|PubMed:19438226};
DE AltName: Full=Carbonate dehydratase 1 {ECO:0000303|PubMed:19317447};
DE AltName: Full=mtCA 1 {ECO:0000303|PubMed:19317447};
GN Name=mtcA1 {ECO:0000303|PubMed:19317447}; Synonyms=canA;
GN OrderedLocusNames=Rv1284; ORFNames=MTCY373.03;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP IDENTIFICATION AS A DRUG TARGET [LARGE SCALE ANALYSIS].
RX PubMed=19099550; DOI=10.1186/1752-0509-2-109;
RA Raman K., Yeturu K., Chandra N.;
RT "targetTB: a target identification pipeline for Mycobacterium tuberculosis
RT through an interactome, reactome and genome-scale structural analysis.";
RL BMC Syst. Biol. 2:109-109(2008).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND NOMENCLATURE.
RX PubMed=19317447; DOI=10.1021/jm9000488;
RA Minakuchi T., Nishimori I., Vullo D., Scozzafava A., Supuran C.T.;
RT "Molecular cloning, characterization, and inhibition studies of the Rv1284
RT beta-carbonic anhydrase from Mycobacterium tuberculosis with sulfonamides
RT and a sulfamate.";
RL J. Med. Chem. 52:2226-2232(2009).
RN [4]
RP CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=19438226; DOI=10.1021/jm9004016;
RA Guzel O., Maresca A., Scozzafava A., Salman A., Balaban A.T., Supuran C.T.;
RT "Discovery of low nanomolar and subnanomolar inhibitors of the
RT mycobacterial beta-carbonic anhydrases Rv1284 and Rv3273.";
RL J. Med. Chem. 52:4063-4067(2009).
RN [5]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT THR-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEX WITH COFACTOR, SUBUNIT,
RP AND COFACTOR.
RX PubMed=15753099; DOI=10.1074/jbc.m414348200;
RA Suarez Covarrubias A., Larsson A.M., Hogbom M., Lindberg J., Bergfors T.,
RA Bjorkelid C., Mowbray S.L., Unge T., Jones T.A.;
RT "Structure and function of carbonic anhydrases from Mycobacterium
RT tuberculosis.";
RL J. Biol. Chem. 280:18782-18789(2005).
CC -!- FUNCTION: Catalyzes the reversible hydration of carbon dioxide to form
CC bicarbonate. {ECO:0000269|PubMed:19317447}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + hydrogencarbonate = CO2 + H2O; Xref=Rhea:RHEA:10748,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:17544; EC=4.2.1.1; Evidence={ECO:0000269|PubMed:19317447,
CC ECO:0000269|PubMed:19438226};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:15753099};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:15753099};
CC -!- ACTIVITY REGULATION: Inhibited by sulfonamides and sulfamates. The best
CC inhibitors are 3-bromosulfanilamide and indisulam.
CC {ECO:0000269|PubMed:19317447, ECO:0000269|PubMed:19438226}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:15753099}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC -!- SIMILARITY: Belongs to the beta-class carbonic anhydrase family.
CC {ECO:0000305}.
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DR EMBL; AL123456; CCP44040.1; -; Genomic_DNA.
DR PIR; H70771; H70771.
DR RefSeq; NP_215800.1; NC_000962.3.
DR RefSeq; WP_003406616.1; NZ_NVQJ01000030.1.
DR PDB; 1YLK; X-ray; 2.00 A; A/B/C/D=2-163.
DR PDB; 4YF4; X-ray; 1.80 A; A/B/C/D=2-163.
DR PDB; 4YF5; X-ray; 2.00 A; A/B/C/D=2-163.
DR PDB; 4YF6; X-ray; 3.00 A; A/B/C/D=2-163.
DR PDBsum; 1YLK; -.
DR PDBsum; 4YF4; -.
DR PDBsum; 4YF5; -.
DR PDBsum; 4YF6; -.
DR AlphaFoldDB; P9WPJ7; -.
DR SMR; P9WPJ7; -.
DR STRING; 83332.Rv1284; -.
DR BindingDB; P9WPJ7; -.
DR ChEMBL; CHEMBL5631; -.
DR DrugCentral; P9WPJ7; -.
DR iPTMnet; P9WPJ7; -.
DR PaxDb; P9WPJ7; -.
DR DNASU; 886987; -.
DR GeneID; 45425256; -.
DR GeneID; 886987; -.
DR KEGG; mtu:Rv1284; -.
DR TubercuList; Rv1284; -.
DR eggNOG; COG0288; Bacteria.
DR OMA; AIFTCMD; -.
DR PhylomeDB; P9WPJ7; -.
DR PRO; PR:P9WPJ7; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0004089; F:carbonate dehydratase activity; IDA:MTBBASE.
DR GO; GO:0008270; F:zinc ion binding; IDA:MTBBASE.
DR Gene3D; 3.40.1050.10; -; 1.
DR InterPro; IPR001765; Carbonic_anhydrase.
DR InterPro; IPR036874; Carbonic_anhydrase_sf.
DR PANTHER; PTHR43175; PTHR43175; 1.
DR Pfam; PF00484; Pro_CA; 1.
DR SMART; SM00947; Pro_CA; 1.
DR SUPFAM; SSF53056; SSF53056; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Lyase; Metal-binding; Reference proteome; Zinc.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:21969609"
FT CHAIN 2..163
FT /note="Beta-carbonic anhydrase 1"
FT /id="PRO_0000103784"
FT BINDING 35
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:15753099"
FT BINDING 37
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:15753099"
FT BINDING 88
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:15753099"
FT BINDING 91
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:15753099"
FT MOD_RES 2
FT /note="N-acetylthreonine"
FT /evidence="ECO:0007744|PubMed:21969609"
FT HELIX 3..16
FT /evidence="ECO:0007829|PDB:1YLK"
FT STRAND 30..35
FT /evidence="ECO:0007829|PDB:1YLK"
FT HELIX 42..46
FT /evidence="ECO:0007829|PDB:1YLK"
FT STRAND 52..58
FT /evidence="ECO:0007829|PDB:1YLK"
FT HELIX 65..76
FT /evidence="ECO:0007829|PDB:1YLK"
FT STRAND 82..90
FT /evidence="ECO:0007829|PDB:1YLK"
FT HELIX 92..94
FT /evidence="ECO:0007829|PDB:1YLK"
FT HELIX 98..109
FT /evidence="ECO:0007829|PDB:1YLK"
FT HELIX 123..135
FT /evidence="ECO:0007829|PDB:1YLK"
FT STRAND 144..151
FT /evidence="ECO:0007829|PDB:1YLK"
FT TURN 153..155
FT /evidence="ECO:0007829|PDB:1YLK"
FT STRAND 158..161
FT /evidence="ECO:0007829|PDB:1YLK"
SQ SEQUENCE 163 AA; 18189 MW; DDD342B7DBFE5AA0 CRC64;
MTVTDDYLAN NVDYASGFKG PLPMPPSKHI AIVACMDARL DVYRMLGIKE GEAHVIRNAG
CVVTDDVIRS LAISQRLLGT REIILLHHTD CGMLTFTDDD FKRAIQDETG IRPTWSPESY
PDAVEDVRQS LRRIEVNPFV TKHTSLRGFV FDVATGKLNE VTP
