{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"P9WJN1","secondaryAccessions":["L7N5N8"],"uniProtkbId":"MCA_MYCTU","entryAudit":{"firstPublicDate":"2014-04-16","lastAnnotationUpdateDate":"2026-06-10","lastSequenceUpdateDate":"2014-04-16","entryVersion":51,"sequenceVersion":1},"annotationScore":5.0,"organism":{"scientificName":"Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)","taxonId":83332,"lineage":["Bacteria","Bacillati","Actinomycetota","Actinomycetes","Mycobacteriales","Mycobacteriaceae","Mycobacterium","Mycobacterium tuberculosis complex"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"evidences":[{"evidenceCode":"ECO:0000255","source":"HAMAP-Rule","id":"MF_01482"}],"value":"Mycothiol S-conjugate amidase"},"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000255","source":"HAMAP-Rule","id":"MF_01482"}],"value":"3.5.1.115"}]}},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000255","source":"HAMAP-Rule","id":"MF_01482"}],"value":"mca"},"orderedLocusNames":[{"value":"Rv1082"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10978158"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14556638"}],"value":"A mycothiol (MSH, N-acetyl-cysteinyl-glucosaminyl-inositol) S-conjugate amidase, it recycles conjugated MSH to the N-acetyl cysteine conjugate and the MSH precursor. Involved in MSH-dependent detoxification of a number of alkylating agents and antibiotics. Activity is specific for the mycothiol moiety. Has a low but measurable deacetylation activity on GlcNAc-Ins (N-acetyl-glucosaminyl-inositol), and thus can also directly contribute to the production of MSH"}],"commentType":"FUNCTION"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"mycothiol S-conjugate + H2O = an N-acetyl-L-cysteine-S-conjugate + 1D-myo-inositol 2-amino-2-deoxy-alpha-D-glucopyranoside","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:36543"},{"database":"ChEBI","id":"CHEBI:15377"},{"database":"ChEBI","id":"CHEBI:58718"},{"database":"ChEBI","id":"CHEBI:58886"},{"database":"ChEBI","id":"CHEBI:59633"}],"ecNumber":"3.5.1.115","evidences":[{"evidenceCode":"ECO:0000255","source":"HAMAP-Rule","id":"MF_01482"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10978158"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14556638"}]}},{"commentType":"COFACTOR","cofactors":[{"name":"Fe(2+)","evidences":[{"evidenceCode":"ECO:0000255","source":"HAMAP-Rule","id":"MF_01482"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26044118"}],"cofactorCrossReference":{"database":"ChEBI","id":"CHEBI:29033"}}],"note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14556638"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26044118"}],"value":"Appears to be a Fe(2+)-dependent enzyme under physiological anaerobic conditions (PubMed:26044118). Binds Zn(2+) under aerobic conditions; this experimental artifact could become biologically relevant under oxidatively stressed conditions, such as those encountered inside activated macrophages (PubMed:14556638, PubMed:26044118)."}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14556638"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18020307"}],"value":"Partially inhibited by MSH when MSmB is used as substrate. Competitively inhibited by the GlcNAc-cyclohexyl derivative 5-(4-chlorophenyl)-N-((2R,3R,4R,5S,6R)-2-(cyclohexylthio)-tetrahydro-4,5-dihydroxy-6-(hydroxymethyl)-2H-pyran-3-yl)furan-2-carboxamide, which also inhibits MshB"}],"commentType":"ACTIVITY REGULATION"},{"commentType":"BIOPHYSICOCHEMICAL PROPERTIES","kineticParameters":{"michaelisConstants":[{"constant":160.0,"unit":"uM","substrate":"MSmB (a bimane derivative of MSH)","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14556638"}]},{"constant":190.0,"unit":"uM","substrate":"RifS13 (reduced MSH S-conjugate of rifamycin S)","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14556638"}]},{"constant":450.0,"unit":"uM","substrate":"RifS17 (oxidized MSH S-conjugate of rifamycin S)","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14556638"}]},{"constant":650.0,"unit":"uM","substrate":"MS-cerulenin (cerulenin S-conjugate of MSH)","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14556638"}]},{"constant":2000.0,"unit":"uM","substrate":"GlcNAc-Ins","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14556638"}]}],"note":{"texts":[{"value":"at 50 mM HEPES, pH 7.5, 37 degrees Celsius, 50 mM NaCl."}]}}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000255","source":"HAMAP-Rule","id":"MF_01482"}],"value":"Monomer"}],"commentType":"SUBUNIT"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18020307"}],"value":"MSH is a glutathione analog and is essential for this organism. As MSH does not exist in its host (human) enzymes that are required for its metabolism (such as this one) are potential therapeutic targets"}],"commentType":"BIOTECHNOLOGY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000255","source":"HAMAP-Rule","id":"MF_01482"}],"value":"Belongs to the MshB deacetylase family. Mca subfamily"}],"commentType":"SIMILARITY"}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":288,"modifier":"EXACT"}},"description":"Mycothiol S-conjugate amidase","featureId":"PRO_0000423187"},{"type":"Binding site","location":{"start":{"value":12,"modifier":"EXACT"},"end":{"value":12,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:29033"}],"evidences":[{"evidenceCode":"ECO:0000255","source":"HAMAP-Rule","id":"MF_01482"}],"ligand":{"name":"Fe(2+)","id":"ChEBI:CHEBI:29033"}},{"type":"Binding site","location":{"start":{"value":15,"modifier":"EXACT"},"end":{"value":15,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:29033"}],"evidences":[{"evidenceCode":"ECO:0000255","source":"HAMAP-Rule","id":"MF_01482"}],"ligand":{"name":"Fe(2+)","id":"ChEBI:CHEBI:29033"}},{"type":"Binding site","location":{"start":{"value":142,"modifier":"EXACT"},"end":{"value":142,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:29033"}],"evidences":[{"evidenceCode":"ECO:0000255","source":"HAMAP-Rule","id":"MF_01482"}],"ligand":{"name":"Fe(2+)","id":"ChEBI:CHEBI:29033"}}],"keywords":[{"id":"KW-0216","category":"Biological process","name":"Detoxification"},{"id":"KW-0378","category":"Molecular function","name":"Hydrolase"},{"id":"KW-0408","category":"Ligand","name":"Iron"},{"id":"KW-0479","category":"Ligand","name":"Metal-binding"},{"id":"KW-1185","category":"Technical term","name":"Reference proteome"}],"references":[{"referenceNumber":1,"citation":{"id":"9634230","citationType":"journal article","authors":["Cole S.T.","Brosch R.","Parkhill J.","Garnier T.","Churcher C.M.","Harris D.E.","Gordon S.V.","Eiglmeier K.","Gas S.","Barry C.E. III","Tekaia F.","Badcock K.","Basham D.","Brown D.","Chillingworth T.","Connor R.","Davies R.M.","Devlin K.","Feltwell T.","Gentles S.","Hamlin N.","Holroyd S.","Hornsby T.","Jagels K.","Krogh A.","McLean J.","Moule S.","Murphy L.D.","Oliver S.","Osborne J.","Quail M.A.","Rajandream M.A.","Rogers J.","Rutter S.","Seeger K.","Skelton S.","Squares S.","Squares R.","Sulston J.E.","Taylor K.","Whitehead S.","Barrell B.G."],"citationCrossReferences":[{"database":"PubMed","id":"9634230"},{"database":"DOI","id":"10.1038/31159"}],"title":"Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence.","publicationDate":"1998","journal":"Nature","firstPage":"537","lastPage":"544","volume":"393"},"referencePositions":["NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]"],"referenceComments":[{"value":"ATCC 25618 / H37Rv","type":"STRAIN"}]},{"referenceNumber":2,"citation":{"id":"10978158","citationType":"journal article","authors":["Newton G.L.","Av-Gay Y.","Fahey R.C."],"citationCrossReferences":[{"database":"PubMed","id":"10978158"},{"database":"DOI","id":"10.1021/bi000356n"}],"title":"A novel mycothiol-dependent detoxification pathway in mycobacteria involving mycothiol S-conjugate amidase.","publicationDate":"2000","journal":"Biochemistry","firstPage":"10739","lastPage":"10746","volume":"39"},"referencePositions":["FUNCTION","CATALYTIC ACTIVITY"],"referenceComments":[{"value":"ATCC 25618 / H37Rv","type":"STRAIN"}]},{"referenceNumber":3,"citation":{"id":"14556638","citationType":"journal article","authors":["Steffek M.","Newton G.L.","Av-Gay Y.","Fahey R.C."],"citationCrossReferences":[{"database":"PubMed","id":"14556638"},{"database":"DOI","id":"10.1021/bi030080u"}],"title":"Characterization of Mycobacterium tuberculosis mycothiol S-conjugate amidase.","publicationDate":"2003","journal":"Biochemistry","firstPage":"12067","lastPage":"12076","volume":"42"},"referencePositions":["FUNCTION","CATALYTIC ACTIVITY","ZINC-BINDING","ACTIVITY REGULATION","BIOPHYSICOCHEMICAL PROPERTIES"],"referenceComments":[{"value":"ATCC 25618 / H37Rv","type":"STRAIN"}]},{"referenceNumber":4,"citation":{"id":"18020307","citationType":"journal article","authors":["Metaferia B.B.","Fetterolf B.J.","Shazad-Ul-Hussan S.","Moravec M.","Smith J.A.","Ray S.","Gutierrez-Lugo M.T.","Bewley C.A."],"citationCrossReferences":[{"database":"PubMed","id":"18020307"},{"database":"DOI","id":"10.1021/jm070669h"}],"title":"Synthesis of natural product-inspired inhibitors of Mycobacterium tuberculosis mycothiol-associated enzymes: the first inhibitors of GlcNAc-Ins deacetylase.","publicationDate":"2007","journal":"J. Med. Chem.","firstPage":"6326","lastPage":"6336","volume":"50"},"referencePositions":["ACTIVITY REGULATION","BIOTECHNOLOGY"]},{"referenceNumber":5,"citation":{"id":"21969609","citationType":"journal article","authors":["Kelkar D.S.","Kumar D.","Kumar P.","Balakrishnan L.","Muthusamy B.","Yadav A.K.","Shrivastava P.","Marimuthu A.","Anand S.","Sundaram H.","Kingsbury R.","Harsha H.C.","Nair B.","Prasad T.S.","Chauhan D.S.","Katoch K.","Katoch V.M.","Kumar P.","Chaerkady R.","Ramachandran S.","Dash D.","Pandey A."],"citationCrossReferences":[{"database":"PubMed","id":"21969609"},{"database":"DOI","id":"10.1074/mcp.m111.011445"}],"title":"Proteogenomic analysis of Mycobacterium tuberculosis by high resolution mass spectrometry.","publicationDate":"2011","journal":"Mol. Cell. Proteomics","firstPage":"M111.011627","lastPage":"M111.011627","volume":"10"},"referencePositions":["IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]"],"referenceComments":[{"value":"ATCC 25618 / H37Rv","type":"STRAIN"}]},{"referenceNumber":6,"citation":{"id":"26044118","citationType":"journal article","authors":["Kocabas E.","Liu H.","Hernick M."],"citationCrossReferences":[{"database":"PubMed","id":"26044118"},{"database":"DOI","id":"10.1007/s10534-015-9864-6"}],"title":"Identity of cofactor bound to mycothiol conjugate amidase (Mca) influenced by expression and purification conditions.","publicationDate":"2015","journal":"BioMetals","firstPage":"755","lastPage":"763","volume":"28"},"referencePositions":["COFACTOR"]}],"uniProtKBCrossReferences":[{"database":"EMBL","id":"AL123456","properties":[{"key":"ProteinId","value":"CCP43833.1"},{"key":"Status","value":"-"},{"key":"MoleculeType","value":"Genomic_DNA"}]},{"database":"PIR","id":"H70894","properties":[{"key":"EntryName","value":"H70894"}]},{"database":"RefSeq","id":"NP_215598.1","properties":[{"key":"NucleotideSequenceId","value":"NC_000962.3"}]},{"database":"RefSeq","id":"WP_003405746.1","properties":[{"key":"NucleotideSequenceId","value":"NC_000962.3"}]},{"database":"AlphaFoldDB","id":"P9WJN1","properties":[{"key":"Description","value":"-"}]},{"database":"SMR","id":"P9WJN1","properties":[{"key":"Description","value":"-"}]},{"database":"FunCoup","id":"P9WJN1","properties":[{"key":"Number of interactors","value":"1"}]},{"database":"STRING","id":"83332.Rv1082","properties":[{"key":"Description","value":"-"}]},{"database":"BindingDB","id":"P9WJN1","properties":[{"key":"Description","value":"-"}]},{"database":"ChEMBL","id":"CHEMBL3703","properties":[{"key":"Description","value":"-"}]},{"database":"PaxDb","id":"83332-Rv1082","properties":[{"key":"Description","value":"-"}]},{"database":"DNASU","id":"887101","properties":[{"key":"Description","value":"-"}]},{"database":"GeneID","id":"45425055","properties":[{"key":"Description","value":"-"}]},{"database":"GeneID","id":"887101","properties":[{"key":"Description","value":"-"}]},{"database":"KEGG","id":"mtu:Rv1082","properties":[{"key":"Description","value":"-"}]},{"database":"KEGG","id":"mtv:RVBD_1082","properties":[{"key":"Description","value":"-"}]},{"database":"TubercuList","id":"Rv1082","properties":[{"key":"Description","value":"-"}]},{"database":"eggNOG","id":"COG2120","properties":[{"key":"ToxonomicScope","value":"Bacteria"}]},{"database":"InParanoid","id":"P9WJN1","properties":[{"key":"Description","value":"-"}]},{"database":"OrthoDB","id":"158614at2","properties":[{"key":"Description","value":"-"}]},{"database":"PhylomeDB","id":"P9WJN1","properties":[{"key":"Description","value":"-"}]},{"database":"BioCyc","id":"MetaCyc:G185E-5244-MONOMER","properties":[{"key":"Description","value":"-"}]},{"database":"BRENDA","id":"3.5.1.115","properties":[{"key":"OrganismId","value":"3445"}]},{"database":"Reactome","id":"R-MTU-879235","properties":[{"key":"PathwayName","value":"Mycothiol-dependent detoxification"}]},{"database":"Reactome","id":"R-MTU-879299","properties":[{"key":"PathwayName","value":"Mycothiol biosynthesis"}]},{"database":"Reactome","id":"R-MTU-879325","properties":[{"key":"PathwayName","value":"Mycothiol catabolism"}]},{"database":"Proteomes","id":"UP000001584","properties":[{"key":"Component","value":"Chromosome"}]},{"database":"AbasyAtlas","id":"P9WJN1","properties":[{"key":"Description","value":"-"}]},{"database":"GO","id":"GO:0005829","properties":[{"key":"GoTerm","value":"C:cytosol"},{"key":"GoEvidenceType","value":"TAS:Reactome"}]},{"database":"GO","id":"GO:0005886","properties":[{"key":"GoTerm","value":"C:plasma membrane"},{"key":"GoEvidenceType","value":"HDA:MTBBASE"}],"evidences":[{"evidenceCode":"ECO:0007005","source":"PubMed","id":"14532352"}]},{"database":"GO","id":"GO:0016810","properties":[{"key":"GoTerm","value":"F:hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds"},{"key":"GoEvidenceType","value":"IDA:MTBBASE"}],"evidences":[{"evidenceCode":"ECO:0000314","source":"PubMed","id":"14556638"}]},{"database":"GO","id":"GO:0016811","properties":[{"key":"GoTerm","value":"F:hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides"},{"key":"GoEvidenceType","value":"IDA:MTBBASE"}],"evidences":[{"evidenceCode":"ECO:0000314","source":"PubMed","id":"10978158"}]},{"database":"GO","id":"GO:0008270","properties":[{"key":"GoTerm","value":"F:zinc ion binding"},{"key":"GoEvidenceType","value":"IDA:UniProtKB"}],"evidences":[{"evidenceCode":"ECO:0000314","source":"PubMed","id":"14556638"}]},{"database":"GO","id":"GO:0010125","properties":[{"key":"GoTerm","value":"P:mycothiol biosynthetic process"},{"key":"GoEvidenceType","value":"IDA:MTBBASE"}],"evidences":[{"evidenceCode":"ECO:0000314","source":"PubMed","id":"10978158"}]},{"database":"GO","id":"GO:0010126","properties":[{"key":"GoTerm","value":"P:mycothiol metabolic process"},{"key":"GoEvidenceType","value":"IDA:UniProtKB"}],"evidences":[{"evidenceCode":"ECO:0000314","source":"PubMed","id":"14556638"}]},{"database":"GO","id":"GO:0010127","properties":[{"key":"GoTerm","value":"P:mycothiol-dependent detoxification"},{"key":"GoEvidenceType","value":"IDA:UniProtKB"}],"evidences":[{"evidenceCode":"ECO:0000314","source":"PubMed","id":"14556638"}]},{"database":"GO","id":"GO:0052167","properties":[{"key":"GoTerm","value":"P:symbiont-mediated perturbation of host innate immune response"},{"key":"GoEvidenceType","value":"IDA:MTBBASE"}],"evidences":[{"evidenceCode":"ECO:0000314","source":"PubMed","id":"21170273"}]},{"database":"FunFam","id":"3.40.50.10320:FF:000001","properties":[{"key":"EntryName","value":"Mycothiol S-conjugate amidase"},{"key":"MatchStatus","value":"1"}]},{"database":"Gene3D","id":"3.40.50.10320","properties":[{"key":"EntryName","value":"LmbE-like"},{"key":"MatchStatus","value":"1"}]},{"database":"HAMAP","id":"MF_01482","properties":[{"key":"EntryName","value":"Mca"},{"key":"MatchStatus","value":"1"}]},{"database":"InterPro","id":"IPR003737","properties":[{"key":"EntryName","value":"GlcNAc_PI_deacetylase-related"}]},{"database":"InterPro","id":"IPR024078","properties":[{"key":"EntryName","value":"LmbE-like_dom_sf"}]},{"database":"InterPro","id":"IPR017811","properties":[{"key":"EntryName","value":"Mca"}]},{"database":"NCBIfam","id":"TIGR03446","properties":[{"key":"EntryName","value":"mycothiol_Mca"},{"key":"MatchStatus","value":"1"}]},{"database":"PANTHER","id":"PTHR12993:SF11","properties":[{"key":"EntryName","value":"N-ACETYLGLUCOSAMINYL-PHOSPHATIDYLINOSITOL DE-N-ACETYLASE"},{"key":"MatchStatus","value":"1"}]},{"database":"PANTHER","id":"PTHR12993","properties":[{"key":"EntryName","value":"N-ACETYLGLUCOSAMINYL-PHOSPHATIDYLINOSITOL DE-N-ACETYLASE-RELATED"},{"key":"MatchStatus","value":"1"}]},{"database":"Pfam","id":"PF02585","properties":[{"key":"EntryName","value":"PIG-L"},{"key":"MatchStatus","value":"1"}]},{"database":"SUPFAM","id":"SSF102588","properties":[{"key":"EntryName","value":"LmbE-like"},{"key":"MatchStatus","value":"1"}]}],"sequence":{"value":"MSELRLMAVHAHPDDESSKGAATLARYADEGHRVLVVTLTGGERGEILNPAMDLPDVHGRIAEIRRDEMTKAAEILGVEHTWLGFVDSGLPKGDLPPPLPDDCFARVPLEVSTEALVRVVREFRPHVMTTYDENGGYPHPDHIRCHQVSVAAYEAAGDFCRFPDAGEPWTVSKLYYVHGFLRERMQMLQDEFARHGQRGPFEQWLAYWDPDHDFLTSRVTTRVECSKYFSQRDDALRAHATQIDPNAEFFAAPLAWQERLWPTEEFELARSRIPARPPETELFAGIEP","length":288,"molWeight":32732,"crc64":"C19E3AAA882892DE","md5":"1C4219252FEF49E8E8C50B6533FE1ED8"},"extraAttributes":{"countByCommentType":{"FUNCTION":1,"CATALYTIC ACTIVITY":1,"COFACTOR":1,"ACTIVITY REGULATION":1,"BIOPHYSICOCHEMICAL PROPERTIES":1,"SUBUNIT":1,"BIOTECHNOLOGY":1,"SIMILARITY":1},"countByFeatureType":{"Chain":1,"Binding site":3},"uniParcId":"UPI00000D5FCD"}}