MSHA_MYCTU
ID MSHA_MYCTU Reviewed; 480 AA.
AC P9WMY7; L0T3R4; P64707; Q11152;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 43.
DE RecName: Full=D-inositol 3-phosphate glycosyltransferase;
DE EC=2.4.1.250 {ECO:0000255|HAMAP-Rule:MF_01695};
DE AltName: Full=N-acetylglucosamine-inositol-phosphate N-acetylglucosaminyltransferase {ECO:0000255|HAMAP-Rule:MF_01695};
DE Short=GlcNAc-Ins-P N-acetylglucosaminyltransferase {ECO:0000255|HAMAP-Rule:MF_01695};
GN Name=mshA {ECO:0000255|HAMAP-Rule:MF_01695, ECO:0000303|PubMed:12754249};
GN OrderedLocusNames=Rv0486; ORFNames=MTCY20G9.12;
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=12754249; DOI=10.1128/jb.185.11.3476-3479.2003;
RA Newton G.L., Koledin T., Gorovitz B., Rawat M., Fahey R.C., Av-Gay Y.;
RT "The glycosyltransferase gene encoding the enzyme catalyzing the first step
RT of mycothiol biosynthesis (mshA).";
RL J. Bacteriol. 185:3476-3479(2003).
RN [3]
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 [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=26774486; DOI=10.1016/j.celrep.2015.12.056;
RA Saini V., Cumming B.M., Guidry L., Lamprecht D.A., Adamson J.H.,
RA Reddy V.P., Chinta K.C., Mazorodze J.H., Glasgow J.N.,
RA Richard-Greenblatt M., Gomez-Velasco A., Bach H., Av-Gay Y., Eoh H.,
RA Rhee K., Steyn A.J.;
RT "Ergothioneine maintains redox and bioenergetic homeostasis essential for
RT drug susceptibility and virulence of Mycobacterium tuberculosis.";
RL Cell Rep. 14:572-585(2016).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=26637353; DOI=10.1074/jbc.m115.684597;
RA Mehta M., Rajmani R.S., Singh A.;
RT "Mycobacterium tuberculosis WhiB3 responds to vacuolar pH-induced changes
RT in mycothiol redox potential to modulate phagosomal maturation and
RT virulence.";
RL J. Biol. Chem. 291:2888-2903(2016).
CC -!- FUNCTION: Catalyzes the transfer of an N-acetyl-glucosamine moiety to
CC 1D-myo-inositol 3-phosphate to produce 1D-myo-inositol 2-acetamido-2-
CC deoxy-glucopyranoside 3-phosphate in the mycothiol (MSH) biosynthesis
CC pathway (PubMed:12754249). MSH and WhiB3 are probably part of a
CC regulatory circuit that mediates gene expression upon acid stress (like
CC that found in host macrophage phagosomes) (PubMed:26637353). MSH is one
CC of the major redox buffers which protects bacteria against redox
CC stressors and antibiotics; loss of MSH or ergothioneine (ERG, the other
CC major redox buffer in this bacteria) leads to respiratory alterations
CC and bioenergetic deficiencies that negatively impact virulence
CC (PubMed:26774486). {ECO:0000269|PubMed:12754249,
CC ECO:0000305|PubMed:26637353, ECO:0000305|PubMed:26774486}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1D-myo-inositol 3-phosphate + UDP-N-acetyl-alpha-D-glucosamine
CC = 1D-myo-inositol 2-acetamido-2-deoxy-alpha-D-glucopyranoside 3-
CC phosphate + H(+) + UDP; Xref=Rhea:RHEA:26188, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57705, ChEBI:CHEBI:58223, ChEBI:CHEBI:58401,
CC ChEBI:CHEBI:58892; EC=2.4.1.250; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_01695};
CC -!- SUBUNIT: Homodimer. {ECO:0000255|HAMAP-Rule:MF_01695}.
CC -!- DISRUPTION PHENOTYPE: Increased intracellular levels of ergothioneine,
CC 8-fold increase in reactive oxygen species-producing cells, decreased
CC resistance to the antibiotics rifampicin, isoniazid, bedaquiline and
CC clofazimine (PubMed:26774486). Increased oxygen consumption and
CC extracellular acidification rates, which are further increased by
CC membrane uncoupler CCCP, indicative of electron chain dysfunction in
CC the absence of MSH (PubMed:26774486). Absence leads to alteration of
CC transcript levels for 139 genes which probably compensate for loss of
CC redox control (PubMed:26774486). Loss of induction of some pH-inducible
CC genes at pH 4.5, including the redox-sensor whiB3 (PubMed:26637353).
CC {ECO:0000269|PubMed:26637353, ECO:0000269|PubMed:26774486}.
CC -!- SIMILARITY: Belongs to the glycosyltransferase group 1 family. MshA
CC subfamily. {ECO:0000305}.
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DR EMBL; AL123456; CCP43220.1; -; Genomic_DNA.
DR PIR; A70744; A70744.
DR RefSeq; NP_215000.1; NC_000962.3.
DR RefSeq; WP_003402367.1; NZ_NVQJ01000002.1.
DR AlphaFoldDB; P9WMY7; -.
DR SMR; P9WMY7; -.
DR STRING; 83332.Rv0486; -.
DR PaxDb; P9WMY7; -.
DR DNASU; 887160; -.
DR GeneID; 887160; -.
DR KEGG; mtu:Rv0486; -.
DR PATRIC; fig|83332.111.peg.533; -.
DR TubercuList; Rv0486; -.
DR eggNOG; COG0438; Bacteria.
DR OMA; HTMAKVK; -.
DR PhylomeDB; P9WMY7; -.
DR Reactome; R-MTU-879299; Mycothiol biosynthesis.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0008375; F:acetylglucosaminyltransferase activity; IDA:MTBBASE.
DR GO; GO:0102710; F:D-inositol-3-phosphate glycosyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0016757; F:glycosyltransferase activity; IBA:GO_Central.
DR GO; GO:0000287; F:magnesium ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0010125; P:mycothiol biosynthetic process; IMP:MTBBASE.
DR HAMAP; MF_01695; MshA; 1.
DR InterPro; IPR001296; Glyco_trans_1.
DR InterPro; IPR028098; Glyco_trans_4-like_N.
DR InterPro; IPR017814; Mycothiol_biosynthesis_MshA.
DR Pfam; PF13439; Glyco_transf_4; 1.
DR Pfam; PF00534; Glycos_transf_1; 1.
DR TIGRFAMs; TIGR03449; mycothiol_MshA; 1.
PE 1: Evidence at protein level;
KW Glycosyltransferase; Magnesium; Metal-binding; Reference proteome;
KW Transferase.
FT CHAIN 1..480
FT /note="D-inositol 3-phosphate glycosyltransferase"
FT /id="PRO_0000080318"
FT REGION 1..42
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 53
FT /ligand="1D-myo-inositol 3-phosphate"
FT /ligand_id="ChEBI:CHEBI:58401"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01695"
FT BINDING 59..60
FT /ligand="UDP-N-acetyl-alpha-D-glucosamine"
FT /ligand_id="ChEBI:CHEBI:57705"
FT /evidence="ECO:0000250"
FT BINDING 64..69
FT /ligand="1D-myo-inositol 3-phosphate"
FT /ligand_id="ChEBI:CHEBI:58401"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01695"
FT BINDING 67
FT /ligand="UDP-N-acetyl-alpha-D-glucosamine"
FT /ligand_id="ChEBI:CHEBI:57705"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01695"
FT BINDING 122
FT /ligand="1D-myo-inositol 3-phosphate"
FT /ligand_id="ChEBI:CHEBI:58401"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01695"
FT BINDING 155
FT /ligand="1D-myo-inositol 3-phosphate"
FT /ligand_id="ChEBI:CHEBI:58401"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01695"
FT BINDING 179
FT /ligand="1D-myo-inositol 3-phosphate"
FT /ligand_id="ChEBI:CHEBI:58401"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01695"
FT BINDING 199
FT /ligand="1D-myo-inositol 3-phosphate"
FT /ligand_id="ChEBI:CHEBI:58401"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01695"
FT BINDING 273
FT /ligand="UDP-N-acetyl-alpha-D-glucosamine"
FT /ligand_id="ChEBI:CHEBI:57705"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01695"
FT BINDING 278
FT /ligand="UDP-N-acetyl-alpha-D-glucosamine"
FT /ligand_id="ChEBI:CHEBI:57705"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01695"
FT BINDING 331
FT /ligand="UDP-N-acetyl-alpha-D-glucosamine"
FT /ligand_id="ChEBI:CHEBI:57705"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01695"
FT BINDING 340
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01695"
FT BINDING 341
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01695"
FT BINDING 343
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01695"
FT BINDING 353
FT /ligand="UDP-N-acetyl-alpha-D-glucosamine"
FT /ligand_id="ChEBI:CHEBI:57705"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01695"
FT BINDING 361
FT /ligand="UDP-N-acetyl-alpha-D-glucosamine"
FT /ligand_id="ChEBI:CHEBI:57705"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01695"
FT BINDING 367
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01695"
SQ SEQUENCE 480 AA; 50541 MW; 2134755E894A9CCF CRC64;
MAGVRHDDGS GLIAQRRPVR GEGATRSRGP SGPSNRNVSA ADDPRRVALL AVHTSPLAQP
GTGDAGGMNV YMLQSALHLA RRGIEVEIFT RATASADPPV VRVAPGVLVR NVVAGPFEGL
DKYDLPTQLC AFAAGVLRAE AVHEPGYYDI VHSHYWLSGQ VGWLARDRWA VPLVHTAHTL
AAVKNAALAD GDGPEPPLRT VGEQQVVDEA DRLIVNTDDE ARQVISLHGA DPARIDVVHP
GVDLDVFRPG DRRAARAALG LPVDERVVAF VGRIQPLKAP DIVLRAAAKL PGVRIIVAGG
PSGSGLASPD GLVRLADELG ISARVTFLPP QSHTDLATLF RAADLVAVPS YSESFGLVAV
EAQACGTPVV AAAVGGLPVA VRDGITGTLV SGHEVGQWAD AIDHLLRLCA GPRGRVMSRA
AARHAATFSW ENTTDALLAS YRRAIGEYNA ERQRRGGEVI SDLVAVGKPR HWTPRRGVGA
