MSHD_MYCTU
ID MSHD_MYCTU Reviewed; 315 AA.
AC P9WJM7; L0T7T7; O53831; Q7D982;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 46.
DE RecName: Full=Mycothiol acetyltransferase;
DE Short=MSH acetyltransferase;
DE EC=2.3.1.189;
DE AltName: Full=Mycothiol synthase;
GN Name=mshD; OrderedLocusNames=Rv0819;
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.
RX PubMed=12375100; DOI=10.1007/s00203-002-0462-y;
RA Koledin T., Newton G.L., Fahey R.C.;
RT "Identification of the mycothiol synthase gene (mshD) encoding the
RT acetyltransferase producing mycothiol in actinomycetes.";
RL Arch. Microbiol. 178:331-337(2002).
RN [3]
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 [4]
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).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) IN COMPLEX WITH COA AND ACETYL-COA,
RP AND SUBUNIT.
RX PubMed=12930994; DOI=10.1110/ps.03153703;
RA Vetting M.W., Roderick S.L., Yu M., Blanchard J.S.;
RT "Crystal structure of mycothiol synthase (Rv0819) from Mycobacterium
RT tuberculosis shows structural homology to the GNAT family of N-
RT acetyltransferases.";
RL Protein Sci. 12:1954-1959(2003).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) IN COMPLEX WITH COA AND
RP DESACETYLMYCOTHIOL, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP REACTION MECHANISM.
RX PubMed=16326705; DOI=10.1074/jbc.m510798200;
RA Vetting M.W., Yu M., Rendle P.M., Blanchard J.S.;
RT "The substrate-induced conformational change of Mycobacterium tuberculosis
RT mycothiol synthase.";
RL J. Biol. Chem. 281:2795-2802(2006).
CC -!- FUNCTION: Catalyzes the transfer of acetyl from acetyl-CoA to
CC desacetylmycothiol (Cys-GlcN-Ins) to form mycothiol.
CC {ECO:0000269|PubMed:12375100}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1D-myo-inositol 2-(L-cysteinylamino)-2-deoxy-alpha-D-
CC glucopyranoside + acetyl-CoA = CoA + H(+) + mycothiol;
CC Xref=Rhea:RHEA:26172, ChEBI:CHEBI:15378, ChEBI:CHEBI:16768,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:58887;
CC EC=2.3.1.189; Evidence={ECO:0000269|PubMed:16326705};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=40 uM for acetyl-CoA {ECO:0000269|PubMed:16326705};
CC KM=82 uM for deacetylmycothiol {ECO:0000269|PubMed:16326705};
CC pH dependence:
CC Optimum pH is 8.2-8.5. {ECO:0000269|PubMed:16326705};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:12930994,
CC ECO:0000269|PubMed:16326705}.
CC -!- MISCELLANEOUS: The N-terminal acetyl-CoA does not function as substrate
CC in the catalyzed reaction, but is believed to have a structural role.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC -!- SIMILARITY: Belongs to the acetyltransferase family. MshD subfamily.
CC {ECO:0000305}.
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DR EMBL; AL123456; CCP43567.1; -; Genomic_DNA.
DR PIR; C70810; C70810.
DR RefSeq; NP_215334.1; NC_000962.3.
DR RefSeq; WP_003404307.1; NZ_NVQJ01000066.1.
DR PDB; 1OZP; X-ray; 1.70 A; A=1-315.
DR PDB; 1P0H; X-ray; 1.60 A; A=1-315.
DR PDB; 2C27; X-ray; 1.80 A; A=1-315.
DR PDBsum; 1OZP; -.
DR PDBsum; 1P0H; -.
DR PDBsum; 2C27; -.
DR AlphaFoldDB; P9WJM7; -.
DR SMR; P9WJM7; -.
DR STRING; 83332.Rv0819; -.
DR DrugBank; DB01992; Coenzyme A.
DR PaxDb; P9WJM7; -.
DR DNASU; 885251; -.
DR GeneID; 885251; -.
DR KEGG; mtu:Rv0819; -.
DR TubercuList; Rv0819; -.
DR eggNOG; COG0454; Bacteria.
DR eggNOG; COG0456; Bacteria.
DR OMA; AEPWFDP; -.
DR PhylomeDB; P9WJM7; -.
DR BioCyc; MetaCyc:G185E-4968-MON; -.
DR BRENDA; 2.3.1.189; 3445.
DR Reactome; R-MTU-879299; Mycothiol biosynthesis.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0016747; F:acyltransferase activity, transferring groups other than amino-acyl groups; IBA:GO_Central.
DR GO; GO:0035447; F:mycothiol synthase activity; IDA:MTBBASE.
DR GO; GO:0008999; F:ribosomal protein S5-alanine N-acetyltransferase activity; IBA:GO_Central.
DR GO; GO:0051701; P:biological process involved in interaction with host; IMP:MTBBASE.
DR GO; GO:0071468; P:cellular response to acidic pH; IMP:UniProtKB.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IMP:UniProtKB.
DR GO; GO:0010125; P:mycothiol biosynthetic process; IDA:MTBBASE.
DR GO; GO:0010126; P:mycothiol metabolic process; IMP:UniProtKB.
DR GO; GO:0017189; P:N-terminal peptidyl-alanine acetylation; IBA:GO_Central.
DR HAMAP; MF_01698; MshD; 1.
DR InterPro; IPR016181; Acyl_CoA_acyltransferase.
DR InterPro; IPR000182; GNAT_dom.
DR InterPro; IPR017813; Mycothiol_AcTrfase.
DR Pfam; PF00583; Acetyltransf_1; 2.
DR PIRSF; PIRSF021524; MSH_acetyltransferase; 1.
DR SUPFAM; SSF55729; SSF55729; 1.
DR TIGRFAMs; TIGR03448; mycothiol_MshD; 1.
DR PROSITE; PS51186; GNAT; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Acyltransferase; Reference proteome; Repeat; Transferase.
FT CHAIN 1..315
FT /note="Mycothiol acetyltransferase"
FT /id="PRO_0000399828"
FT DOMAIN 4..141
FT /note="N-acetyltransferase 1"
FT DOMAIN 152..315
FT /note="N-acetyltransferase 2"
FT BINDING 36
FT /ligand="1D-myo-inositol 2-(L-cysteinylamino)-2-deoxy-
FT alpha-D-glucopyranoside"
FT /ligand_id="ChEBI:CHEBI:58887"
FT /evidence="ECO:0000269|PubMed:16326705"
FT BINDING 80..82
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /ligand_label="1"
FT BINDING 88..93
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /ligand_label="1"
FT BINDING 179
FT /ligand="1D-myo-inositol 2-(L-cysteinylamino)-2-deoxy-
FT alpha-D-glucopyranoside"
FT /ligand_id="ChEBI:CHEBI:58887"
FT /evidence="ECO:0000269|PubMed:16326705"
FT BINDING 224
FT /ligand="1D-myo-inositol 2-(L-cysteinylamino)-2-deoxy-
FT alpha-D-glucopyranoside"
FT /ligand_id="ChEBI:CHEBI:58887"
FT /evidence="ECO:0000269|PubMed:16326705"
FT BINDING 234
FT /ligand="1D-myo-inositol 2-(L-cysteinylamino)-2-deoxy-
FT alpha-D-glucopyranoside"
FT /ligand_id="ChEBI:CHEBI:58887"
FT /evidence="ECO:0000269|PubMed:16326705"
FT BINDING 238..240
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /ligand_label="2"
FT BINDING 245..251
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /ligand_label="2"
FT BINDING 282
FT /ligand="1D-myo-inositol 2-(L-cysteinylamino)-2-deoxy-
FT alpha-D-glucopyranoside"
FT /ligand_id="ChEBI:CHEBI:58887"
FT /evidence="ECO:0000269|PubMed:16326705"
FT BINDING 287..292
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /ligand_label="2"
FT STRAND 7..9
FT /evidence="ECO:0007829|PDB:2C27"
FT HELIX 12..29
FT /evidence="ECO:0007829|PDB:1P0H"
FT HELIX 36..41
FT /evidence="ECO:0007829|PDB:1P0H"
FT STRAND 44..53
FT /evidence="ECO:0007829|PDB:1P0H"
FT STRAND 61..68
FT /evidence="ECO:0007829|PDB:1P0H"
FT STRAND 77..82
FT /evidence="ECO:0007829|PDB:1P0H"
FT HELIX 84..86
FT /evidence="ECO:0007829|PDB:1P0H"
FT STRAND 88..90
FT /evidence="ECO:0007829|PDB:1P0H"
FT HELIX 91..102
FT /evidence="ECO:0007829|PDB:1P0H"
FT TURN 103..105
FT /evidence="ECO:0007829|PDB:1P0H"
FT STRAND 108..111
FT /evidence="ECO:0007829|PDB:1P0H"
FT HELIX 112..114
FT /evidence="ECO:0007829|PDB:1P0H"
FT HELIX 116..124
FT /evidence="ECO:0007829|PDB:1P0H"
FT STRAND 128..142
FT /evidence="ECO:0007829|PDB:1P0H"
FT STRAND 152..156
FT /evidence="ECO:0007829|PDB:1P0H"
FT HELIX 160..162
FT /evidence="ECO:0007829|PDB:1P0H"
FT HELIX 163..173
FT /evidence="ECO:0007829|PDB:1P0H"
FT TURN 174..176
FT /evidence="ECO:0007829|PDB:1P0H"
FT TURN 178..180
FT /evidence="ECO:0007829|PDB:1P0H"
FT HELIX 185..192
FT /evidence="ECO:0007829|PDB:1P0H"
FT HELIX 199..201
FT /evidence="ECO:0007829|PDB:1P0H"
FT STRAND 202..207
FT /evidence="ECO:0007829|PDB:1P0H"
FT STRAND 211..213
FT /evidence="ECO:0007829|PDB:2C27"
FT STRAND 217..224
FT /evidence="ECO:0007829|PDB:1P0H"
FT STRAND 232..240
FT /evidence="ECO:0007829|PDB:1P0H"
FT HELIX 242..244
FT /evidence="ECO:0007829|PDB:1P0H"
FT STRAND 246..248
FT /evidence="ECO:0007829|PDB:1P0H"
FT HELIX 249..264
FT /evidence="ECO:0007829|PDB:1P0H"
FT STRAND 278..284
FT /evidence="ECO:0007829|PDB:1P0H"
FT HELIX 288..296
FT /evidence="ECO:0007829|PDB:1P0H"
FT STRAND 300..309
FT /evidence="ECO:0007829|PDB:1P0H"
SQ SEQUENCE 315 AA; 33599 MW; E1728C0652CF2716 CRC64;
MTALDWRSAL TADEQRSVRA LVTATTAVDG VAPVGEQVLR ELGQQRTEHL LVAGSRPGGP
IIGYLNLSPP RGAGGAMAEL VVHPQSRRRG IGTAMARAAL AKTAGRNQFW AHGTLDPARA
TASALGLVGV RELIQMRRPL RDIPEPTIPD GVVIRTYAGT SDDAELLRVN NAAFAGHPEQ
GGWTAVQLAE RRGEAWFDPD GLILAFGDSP RERPGRLLGF HWTKVHPDHP GLGEVYVLGV
DPAAQRRGLG QMLTSIGIVS LARRLGGRKT LDPAVEPAVL LYVESDNVAA VRTYQSLGFT
TYSVDTAYAL AGTDN
