MCA_MYCTU
ID MCA_MYCTU Reviewed; 288 AA.
AC P9WJN1; L7N5N8;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 37.
DE RecName: Full=Mycothiol S-conjugate amidase {ECO:0000255|HAMAP-Rule:MF_01482};
DE EC=3.5.1.115 {ECO:0000255|HAMAP-Rule:MF_01482};
GN Name=mca {ECO:0000255|HAMAP-Rule:MF_01482}; OrderedLocusNames=Rv1082;
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 FUNCTION, AND CATALYTIC ACTIVITY.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=10978158; DOI=10.1021/bi000356n;
RA Newton G.L., Av-Gay Y., Fahey R.C.;
RT "A novel mycothiol-dependent detoxification pathway in mycobacteria
RT involving mycothiol S-conjugate amidase.";
RL Biochemistry 39:10739-10746(2000).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=14556638; DOI=10.1021/bi030080u;
RA Steffek M., Newton G.L., Av-Gay Y., Fahey R.C.;
RT "Characterization of Mycobacterium tuberculosis mycothiol S-conjugate
RT amidase.";
RL Biochemistry 42:12067-12076(2003).
RN [4]
RP ACTIVITY REGULATION, AND BIOTECHNOLOGY.
RX PubMed=18020307; DOI=10.1021/jm070669h;
RA Metaferia B.B., Fetterolf B.J., Shazad-Ul-Hussan S., Moravec M.,
RA Smith J.A., Ray S., Gutierrez-Lugo M.T., Bewley C.A.;
RT "Synthesis of natural product-inspired inhibitors of Mycobacterium
RT tuberculosis mycothiol-associated enzymes: the first inhibitors of GlcNAc-
RT Ins deacetylase.";
RL J. Med. Chem. 50:6326-6336(2007).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [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).
CC -!- FUNCTION: A mycothiol (MSH, N-acetyl-cysteinyl-glucosaminyl-inositol)
CC S-conjugate amidase, it recycles conjugated MSH to the N-acetyl
CC cysteine conjugate and the MSH precursor. Involved in MSH-dependent
CC detoxification of a number of alkylating agents and antibiotics.
CC Activity is specific for the mycothiol moiety. Has a low but measurable
CC deacetylation activity on GlcNAc-Ins (N-acetyl-glucosaminyl-inositol),
CC and thus can also directly contribute to the production of MSH.
CC {ECO:0000269|PubMed:10978158, ECO:0000269|PubMed:14556638}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + mycothiol S-conjugate = 1D-myo-inositol 2-amino-2-deoxy-
CC alpha-D-glucopyranoside + an N-acetyl-L-cysteine-S-conjugate;
CC Xref=Rhea:RHEA:36543, ChEBI:CHEBI:15377, ChEBI:CHEBI:58718,
CC ChEBI:CHEBI:58886, ChEBI:CHEBI:59633; EC=3.5.1.115;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01482,
CC ECO:0000269|PubMed:10978158, ECO:0000269|PubMed:14556638};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01482,
CC ECO:0000269|PubMed:14556638};
CC Note=Binds 1 Zn(2+) ion per subunit. {ECO:0000255|HAMAP-Rule:MF_01482,
CC ECO:0000269|PubMed:14556638};
CC -!- ACTIVITY REGULATION: Partially inhibited by MSH when MSmB is used as
CC substrate. Competitively inhibited by the GlcNAc-cyclohexyl derivative
CC 5-(4-chlorophenyl)-N-((2R,3R,4R,5S,6R)-2-(cyclohexylthio)-tetrahydro-
CC 4,5-dihydroxy-6-(hydroxymethyl)-2H-pyran-3-yl)furan-2-carboxamide,
CC which also inhibits MshB. {ECO:0000269|PubMed:14556638,
CC ECO:0000269|PubMed:18020307}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=160 uM for MSmB (a bimane derivative of MSH)
CC {ECO:0000269|PubMed:14556638};
CC KM=190 uM for RifS13 (reduced MSH S-conjugate of rifamycin S)
CC {ECO:0000269|PubMed:14556638};
CC KM=450 uM for RifS17 (oxidized MSH S-conjugate of rifamycin S)
CC {ECO:0000269|PubMed:14556638};
CC KM=650 uM for MS-cerulenin (cerulenin S-conjugate of MSH)
CC {ECO:0000269|PubMed:14556638};
CC KM=2000 uM for GlcNAc-Ins {ECO:0000269|PubMed:14556638};
CC Note=at 50 mM HEPES, pH 7.5, 37 degrees Celsius, 50 mM NaCl.;
CC -!- SUBUNIT: Monomer. {ECO:0000255|HAMAP-Rule:MF_01482}.
CC -!- BIOTECHNOLOGY: MSH is a glutathione analog and is essential for this
CC organism. As MSH does not exist in its host (human) enzymes that are
CC required for its metabolism (such as this one) are potential
CC therapeutic targets. {ECO:0000269|PubMed:18020307}.
CC -!- SIMILARITY: Belongs to the MshB deacetylase family. Mca subfamily.
CC {ECO:0000255|HAMAP-Rule:MF_01482}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AL123456; CCP43833.1; -; Genomic_DNA.
DR PIR; H70894; H70894.
DR RefSeq; NP_215598.1; NC_000962.3.
DR RefSeq; WP_003405746.1; NZ_NVQJ01000080.1.
DR AlphaFoldDB; P9WJN1; -.
DR SMR; P9WJN1; -.
DR STRING; 83332.Rv1082; -.
DR BindingDB; P9WJN1; -.
DR ChEMBL; CHEMBL3703; -.
DR PaxDb; P9WJN1; -.
DR DNASU; 887101; -.
DR GeneID; 45425055; -.
DR GeneID; 887101; -.
DR KEGG; mtu:Rv1082; -.
DR TubercuList; Rv1082; -.
DR eggNOG; COG2120; Bacteria.
DR OMA; PLKLYYN; -.
DR PhylomeDB; P9WJN1; -.
DR BioCyc; MetaCyc:G185E-5244-MON; -.
DR BRENDA; 3.5.1.115; 3445.
DR Reactome; R-MTU-879235; Mycothiol-dependent detoxification.
DR Reactome; R-MTU-879299; Mycothiol biosynthesis.
DR Reactome; R-MTU-879325; Mycothiol catabolism.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0016810; F:hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds; IDA:MTBBASE.
DR GO; GO:0016811; F:hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides; IDA:MTBBASE.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0052559; P:induction by symbiont of host immune response; IDA:MTBBASE.
DR GO; GO:0010125; P:mycothiol biosynthetic process; IDA:MTBBASE.
DR GO; GO:0010126; P:mycothiol metabolic process; IDA:UniProtKB.
DR GO; GO:0010127; P:mycothiol-dependent detoxification; IDA:UniProtKB.
DR Gene3D; 3.40.50.10320; -; 1.
DR HAMAP; MF_01482; Mca; 1.
DR InterPro; IPR003737; GlcNAc_PI_deacetylase-related.
DR InterPro; IPR024078; LmbE-like_dom_sf.
DR InterPro; IPR017811; Mca.
DR PANTHER; PTHR12993; PTHR12993; 1.
DR PANTHER; PTHR12993:SF16; PTHR12993:SF16; 1.
DR Pfam; PF02585; PIG-L; 1.
DR SUPFAM; SSF102588; SSF102588; 1.
DR TIGRFAMs; TIGR03446; mycothiol_Mca; 1.
PE 1: Evidence at protein level;
KW Hydrolase; Metal-binding; Reference proteome; Zinc.
FT CHAIN 1..288
FT /note="Mycothiol S-conjugate amidase"
FT /id="PRO_0000423187"
FT BINDING 12
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01482"
FT BINDING 15
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01482"
FT BINDING 142
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01482"
SQ SEQUENCE 288 AA; 32732 MW; C19E3AAA882892DE CRC64;
MSELRLMAVH AHPDDESSKG AATLARYADE GHRVLVVTLT GGERGEILNP AMDLPDVHGR
IAEIRRDEMT KAAEILGVEH TWLGFVDSGL PKGDLPPPLP DDCFARVPLE VSTEALVRVV
REFRPHVMTT YDENGGYPHP DHIRCHQVSV AAYEAAGDFC RFPDAGEPWT VSKLYYVHGF
LRERMQMLQD EFARHGQRGP FEQWLAYWDP DHDFLTSRVT TRVECSKYFS QRDDALRAHA
TQIDPNAEFF AAPLAWQERL WPTEEFELAR SRIPARPPET ELFAGIEP
