MCA_MYCS2
ID MCA_MYCS2 Reviewed; 288 AA.
AC A0R2W9;
DT 24-JUL-2013, integrated into UniProtKB/Swiss-Prot.
DT 09-JAN-2007, sequence version 1.
DT 03-AUG-2022, entry version 85.
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};
GN OrderedLocusNames=MSMEG_5261, MSMEI_5123;
OS Mycolicibacterium smegmatis (strain ATCC 700084 / mc(2)155) (Mycobacterium
OS smegmatis).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycolicibacterium.
OX NCBI_TaxID=246196;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700084 / mc(2)155;
RA Fleischmann R.D., Dodson R.J., Haft D.H., Merkel J.S., Nelson W.C.,
RA Fraser C.M.;
RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=17295914; DOI=10.1186/gb-2007-8-2-r20;
RA Deshayes C., Perrodou E., Gallien S., Euphrasie D., Schaeffer C.,
RA Van-Dorsselaer A., Poch O., Lecompte O., Reyrat J.-M.;
RT "Interrupted coding sequences in Mycobacterium smegmatis: authentic
RT mutations or sequencing errors?";
RL Genome Biol. 8:R20.1-R20.9(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=18955433; DOI=10.1101/gr.081901.108;
RA Gallien S., Perrodou E., Carapito C., Deshayes C., Reyrat J.-M.,
RA Van Dorsselaer A., Poch O., Schaeffer C., Lecompte O.;
RT "Ortho-proteogenomics: multiple proteomes investigation through orthology
RT and a new MS-based protocol.";
RL Genome Res. 19:128-135(2009).
RN [4]
RP PROTEIN SEQUENCE OF 2-20, FUNCTION, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND SUBUNIT.
RC STRAIN=ATCC 700084 / mc(2)155;
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 [5]
RP DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=15342574; DOI=10.1128/jb.186.18.6050-6058.2004;
RA Rawat M., Uppal M., Newton G., Steffek M., Fahey R.C., Av-Gay Y.;
RT "Targeted mutagenesis of the Mycobacterium smegmatis mca gene, encoding a
RT mycothiol-dependent detoxification protein.";
RL J. Bacteriol. 186:6050-6058(2004).
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.
CC {ECO:0000269|PubMed:10978158}.
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 -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01482};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000255|HAMAP-Rule:MF_01482};
CC -!- ACTIVITY REGULATION: Partially inhibited by MSH when MSmB (a bimane
CC derivative of MSH) is used as substrate. {ECO:0000269|PubMed:10978158}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=95 uM for MSmB {ECO:0000269|PubMed:10978158};
CC Note=at 25 mM HEPES, pH 7.5, 30 degrees Celsius.;
CC pH dependence:
CC Optimum pH is 7-9. {ECO:0000269|PubMed:10978158};
CC -!- SUBUNIT: Monomer. {ECO:0000255|HAMAP-Rule:MF_01482,
CC ECO:0000269|PubMed:10978158}.
CC -!- DISRUPTION PHENOTYPE: Loss of amidase activity on MSmB, no production
CC of the mercapturic acid product AcCys-mB. Limited degradation of MS-
CC RifSV, a rifamycin S MSH conjugate. Increased sensitivity to
CC streptomycin, slight increase in sensitivity to rifamycin but no other
CC antibiotics tested. Increased sensitivity to iodoacetamide, N-
CC ethylmalemide (NEM) and redox cycling (oxidant) agents known to
CC conjugate with MSH such as menadione and plumbagin, but not other
CC oxidants. {ECO:0000269|PubMed:15342574}.
CC -!- SIMILARITY: Belongs to the MshB deacetylase family. Mca subfamily.
CC {ECO:0000255|HAMAP-Rule:MF_01482}.
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DR EMBL; CP000480; ABK75043.1; -; Genomic_DNA.
DR EMBL; CP001663; AFP41567.1; -; Genomic_DNA.
DR RefSeq; WP_003896662.1; NZ_SIJM01000014.1.
DR RefSeq; YP_889507.1; NC_008596.1.
DR AlphaFoldDB; A0R2W9; -.
DR SMR; A0R2W9; -.
DR STRING; 246196.MSMEI_5123; -.
DR EnsemblBacteria; ABK75043; ABK75043; MSMEG_5261.
DR EnsemblBacteria; AFP41567; AFP41567; MSMEI_5123.
DR GeneID; 66736575; -.
DR KEGG; msg:MSMEI_5123; -.
DR KEGG; msm:MSMEG_5261; -.
DR PATRIC; fig|246196.19.peg.5132; -.
DR eggNOG; COG2120; Bacteria.
DR OMA; PLKLYYN; -.
DR OrthoDB; 1282433at2; -.
DR SABIO-RK; A0R2W9; -.
DR Proteomes; UP000000757; Chromosome.
DR Proteomes; UP000006158; Chromosome.
DR GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR GO; GO:0008270; F:zinc ion binding; IEA:UniProtKB-UniRule.
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 Direct protein sequencing; Hydrolase; Metal-binding; Reference proteome;
KW Zinc.
FT CHAIN 1..288
FT /note="Mycothiol S-conjugate amidase"
FT /id="PRO_0000423186"
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; 32674 MW; 4586CEF5D75E44F6 CRC64;
MSELRLMAVH AHPDDESSKG AATTARYAAE GARVMVVTLT GGERGDILNP AMDLPEVHGR
IAEVRRDEMA KAAEILGVEH HWLGFVDSGL PEGDPLPPLP DGCFALVPLE EPVKRLVRVI
REFRPHVMTT YDENGGYPHP DHIRCHQVSV AAYEAAADHL LYPDAGEPWA VQKLYYNHGF
LRQRMQLLQE EFAKNGQEGP FAKWLEHWDP DNDVFANRVT TRVHCAEYFH QRDDALRAHA
TQIDPKGDFF HAPIEWQQRL WPTEEFELAR ARVPVTLPED DLFKGVEP
