MSHB_MYCTU
ID MSHB_MYCTU Reviewed; 303 AA.
AC P9WJN3; L0T5W7; O50426; Q7D8Q0;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 40.
DE RecName: Full=1D-myo-inositol 2-acetamido-2-deoxy-alpha-D-glucopyranoside deacetylase;
DE Short=GlcNAc-Ins deacetylase;
DE EC=3.5.1.103;
DE AltName: Full=N-acetyl-1-D-myo-inositol 2-amino-2-deoxy-alpha-D-glucopyranoside deacetylase;
GN Name=mshB; OrderedLocusNames=Rv1170;
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.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=11092856; DOI=10.1128/jb.182.24.6958-6963.2000;
RA Newton G.L., Av-Gay Y., Fahey R.C.;
RT "N-Acetyl-1-D-myo-inosityl-2-amino-2-deoxy-alpha-D-glucopyranoside
RT deacetylase (MshB) is a key enzyme in mycothiol biosynthesis.";
RL J. Bacteriol. 182:6958-6963(2000).
RN [3]
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBSTRATE SPECIFICITY, COFACTOR, AND
RP SUBUNIT.
RX PubMed=16630724; DOI=10.1016/j.pep.2006.03.003;
RA Newton G.L., Ko M., Ta P., Av-Gay Y., Fahey R.C.;
RT "Purification and characterization of Mycobacterium tuberculosis 1D-myo-
RT inosityl-2-acetamido-2-deoxy-alpha-D-glucopyranoside deacetylase, MshB, a
RT mycothiol biosynthetic enzyme.";
RL Protein Expr. Purif. 47:542-550(2006).
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 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 [6]
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 [7]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) IN COMPLEX WITH ZINC, COFACTOR, AND
RP REACTION MECHANISM.
RX PubMed=12958317; DOI=10.1074/jbc.m308914200;
RA Maynes J.T., Garen C., Cherney M.M., Newton G., Arad D., Av-Gay Y.,
RA Fahey R.C., James M.N.G.;
RT "The crystal structure of 1-D-myo-inosityl 2-acetamido-2-deoxy-alpha-D-
RT glucopyranoside deacetylase (MshB) from Mycobacterium tuberculosis reveals
RT a zinc hydrolase with a lactate dehydrogenase fold.";
RL J. Biol. Chem. 278:47166-47170(2003).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH OCTYLGLUCOSIDE.
RX PubMed=14698305; DOI=10.1016/j.jmb.2003.11.034;
RA McCarthy A.A., Peterson N.A., Knijff R., Baker E.N.;
RT "Crystal structure of MshB from Mycobacterium tuberculosis, a deacetylase
RT involved in mycothiol biosynthesis.";
RL J. Mol. Biol. 335:1131-1141(2004).
CC -!- FUNCTION: Catalyzes the deacetylation of 1D-myo-inositol 2-acetamido-2-
CC deoxy-alpha-D-glucopyranoside (GlcNAc-Ins) in the mycothiol (MSH)
CC biosynthesis pathway. Shows some amidase activity toward S-conjugates
CC of mycothiol. {ECO:0000269|PubMed:11092856}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1D-myo-inositol 2-acetamido-2-deoxy-alpha-D-glucopyranoside +
CC H2O = 1D-myo-inositol 2-amino-2-deoxy-alpha-D-glucopyranoside +
CC acetate; Xref=Rhea:RHEA:26180, ChEBI:CHEBI:15377, ChEBI:CHEBI:30089,
CC ChEBI:CHEBI:52442, ChEBI:CHEBI:58886; EC=3.5.1.103;
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:12958317, ECO:0000269|PubMed:16630724};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:12958317,
CC ECO:0000269|PubMed:16630724};
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 Mca. {ECO:0000269|PubMed:18020307}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=340 uM for GlcNAc-Ins {ECO:0000269|PubMed:16630724};
CC KM=500 uM for MSmB {ECO:0000269|PubMed:16630724};
CC KM=134 uM for CySmB-GlcNAc-Ins {ECO:0000269|PubMed:16630724};
CC Vmax=960 nmol/min/mg enzyme with MSmB as substrate
CC {ECO:0000269|PubMed:16630724};
CC Vmax=330 nmol/min/mg enzyme with CySmB-GlcNAc-Ins as substrate
CC {ECO:0000269|PubMed:16630724};
CC Vmax=2820 nmol/min/mg enzyme with GlcNAc-Ins as substrate
CC {ECO:0000269|PubMed:16630724};
CC Note=MSmB is a monobromobimane derivative of mycothiol, CySmB-GlcNAc-
CC Ins is a bimane derivative of mycothiol.;
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:12958317,
CC ECO:0000269|PubMed:14698305, ECO:0000269|PubMed:16630724}.
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 -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC -!- SIMILARITY: Belongs to the MshB deacetylase family. {ECO:0000305}.
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DR EMBL; AL123456; CCP43926.1; -; Genomic_DNA.
DR PIR; B70875; B70875.
DR RefSeq; NP_215686.1; NC_000962.3.
DR RefSeq; WP_003406154.1; NZ_NVQJ01000025.1.
DR PDB; 1Q74; X-ray; 1.70 A; A/B/C/D=1-303.
DR PDB; 1Q7T; X-ray; 1.90 A; A/B=1-303.
DR PDB; 4EWL; X-ray; 1.85 A; A/B=1-299.
DR PDBsum; 1Q74; -.
DR PDBsum; 1Q7T; -.
DR PDBsum; 4EWL; -.
DR AlphaFoldDB; P9WJN3; -.
DR SMR; P9WJN3; -.
DR STRING; 83332.Rv1170; -.
DR BindingDB; P9WJN3; -.
DR ChEMBL; CHEMBL6067; -.
DR PaxDb; P9WJN3; -.
DR GeneID; 45425142; -.
DR GeneID; 885997; -.
DR KEGG; mtu:Rv1170; -.
DR TubercuList; Rv1170; -.
DR eggNOG; COG2120; Bacteria.
DR OMA; YWNRVPR; -.
DR PhylomeDB; P9WJN3; -.
DR BioCyc; MetaCyc:G185E-5339-MON; -.
DR BRENDA; 3.2.2.16; 3445.
DR BRENDA; 3.5.1.103; 3445.
DR PRO; PR:P9WJN3; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0016811; F:hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides; IDA:MTBBASE.
DR GO; GO:0035595; F:N-acetylglucosaminylinositol deacetylase activity; IEA:UniProtKB-EC.
DR GO; GO:0008270; F:zinc ion binding; IDA:MTBBASE.
DR GO; GO:0010125; P:mycothiol biosynthetic process; IDA:MTBBASE.
DR Gene3D; 3.40.50.10320; -; 1.
DR HAMAP; MF_01696; MshB; 1.
DR InterPro; IPR003737; GlcNAc_PI_deacetylase-related.
DR InterPro; IPR024078; LmbE-like_dom_sf.
DR InterPro; IPR017810; Mycothiol_biosynthesis_MshB.
DR PANTHER; PTHR12993; PTHR12993; 1.
DR Pfam; PF02585; PIG-L; 1.
DR SUPFAM; SSF102588; SSF102588; 1.
DR TIGRFAMs; TIGR03445; mycothiol_MshB; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Hydrolase; Metal-binding; Reference proteome; Zinc.
FT CHAIN 1..303
FT /note="1D-myo-inositol 2-acetamido-2-deoxy-alpha-D-
FT glucopyranoside deacetylase"
FT /id="PRO_0000399826"
FT BINDING 13
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:12958317"
FT BINDING 16
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:12958317"
FT BINDING 147
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:12958317"
FT STRAND 6..13
FT /evidence="ECO:0007829|PDB:1Q74"
FT HELIX 16..30
FT /evidence="ECO:0007829|PDB:1Q74"
FT STRAND 34..40
FT /evidence="ECO:0007829|PDB:1Q74"
FT STRAND 49..51
FT /evidence="ECO:0007829|PDB:1Q74"
FT HELIX 54..56
FT /evidence="ECO:0007829|PDB:1Q74"
FT TURN 58..61
FT /evidence="ECO:0007829|PDB:1Q74"
FT HELIX 64..78
FT /evidence="ECO:0007829|PDB:1Q74"
FT STRAND 92..94
FT /evidence="ECO:0007829|PDB:1Q74"
FT STRAND 98..101
FT /evidence="ECO:0007829|PDB:1Q7T"
FT HELIX 109..111
FT /evidence="ECO:0007829|PDB:1Q74"
FT HELIX 114..128
FT /evidence="ECO:0007829|PDB:1Q74"
FT STRAND 131..136
FT /evidence="ECO:0007829|PDB:1Q74"
FT TURN 138..142
FT /evidence="ECO:0007829|PDB:1Q74"
FT HELIX 145..162
FT /evidence="ECO:0007829|PDB:1Q74"
FT STRAND 168..171
FT /evidence="ECO:0007829|PDB:4EWL"
FT STRAND 178..184
FT /evidence="ECO:0007829|PDB:1Q74"
FT HELIX 187..196
FT /evidence="ECO:0007829|PDB:1Q74"
FT HELIX 199..201
FT /evidence="ECO:0007829|PDB:1Q74"
FT HELIX 211..213
FT /evidence="ECO:0007829|PDB:1Q74"
FT STRAND 216..218
FT /evidence="ECO:0007829|PDB:1Q7T"
FT HELIX 220..222
FT /evidence="ECO:0007829|PDB:1Q74"
FT STRAND 225..228
FT /evidence="ECO:0007829|PDB:1Q74"
FT HELIX 231..243
FT /evidence="ECO:0007829|PDB:1Q74"
FT TURN 245..247
FT /evidence="ECO:0007829|PDB:1Q74"
FT STRAND 254..258
FT /evidence="ECO:0007829|PDB:1Q74"
FT STRAND 263..266
FT /evidence="ECO:0007829|PDB:1Q74"
FT STRAND 269..278
FT /evidence="ECO:0007829|PDB:1Q74"
FT TURN 292..295
FT /evidence="ECO:0007829|PDB:1Q74"
FT STRAND 298..300
FT /evidence="ECO:0007829|PDB:1Q7T"
SQ SEQUENCE 303 AA; 31742 MW; 09824FF2C02FB3C7 CRC64;
MSETPRLLFV HAHPDDESLS NGATIAHYTS RGAQVHVVTC TLGEEGEVIG DRWAQLTADH
ADQLGGYRIG ELTAALRALG VSAPIYLGGA GRWRDSGMAG TDQRSQRRFV DADPRQTVGA
LVAIIRELRP HVVVTYDPNG GYGHPDHVHT HTVTTAAVAA AGVGSGTADH PGDPWTVPKF
YWTVLGLSAL ISGARALVPD DLRPEWVLPR ADEIAFGYSD DGIDAVVEAD EQARAAKVAA
LAAHATQVVV GPTGRAAALS NNLALPILAD EHYVLAGGSA GARDERGWET DLLAGLGFTA
SGT
