GPGS_MYCTU
ID GPGS_MYCTU Reviewed; 324 AA.
AC P9WMW9; F2GFY0; L0T8Q4; O05309; Q7D8M0;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 38.
DE RecName: Full=Glucosyl-3-phosphoglycerate synthase {ECO:0000303|PubMed:19015727};
DE Short=GpgS {ECO:0000305};
DE EC=2.4.1.266 {ECO:0000269|PubMed:22637481};
DE AltName: Full=Retaining glucosyltransferase {ECO:0000303|PubMed:22637481};
GN Name=gpgS; OrderedLocusNames=Rv1208;
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 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 [3] {ECO:0007744|PDB:3E25, ECO:0007744|PDB:3E26}
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) IN COMPLEXES WITH
RP 3-PHOSPHO-D-GLYCERATE; UDP AND MAGNESIUM ION, AND SUBUNIT.
RX PubMed=19015727; DOI=10.1371/journal.pone.0003748;
RA Pereira P.J., Empadinhas N., Albuquerque L., Sa-Moura B., da Costa M.S.,
RA Macedo-Ribeiro S.;
RT "Mycobacterium tuberculosis glucosyl-3-phosphoglycerate synthase: structure
RT of a key enzyme in methylglucose lipopolysaccharide biosynthesis.";
RL PLoS ONE 3:E3748-E3748(2008).
RN [4] {ECO:0007744|PDB:4DDZ, ECO:0007744|PDB:4DE7, ECO:0007744|PDB:4DEC}
RP X-RAY CRYSTALLOGRAPHY (1.98 ANGSTROMS) IN COMPLEXES WITH UDP;
RP 3-PHOSPHO-D-GLYCERATE AND MANGANESE ION, FUNCTION, CATALYTIC ACTIVITY,
RP COFACTOR, SUBUNIT, AND REACTION MECHANISM.
RX PubMed=22637481; DOI=10.1074/jbc.m112.368191;
RA Urresti S., Albesa-Jove D., Schaeffer F., Pham H.T., Kaur D., Gest P.,
RA van der Woerd M.J., Carreras-Gonzalez A., Lopez-Fernandez S., Alzari P.M.,
RA Brennan P.J., Jackson M., Guerin M.E.;
RT "Mechanistic insights into the retaining glucosyl-3-phosphoglycerate
RT synthase from mycobacteria.";
RL J. Biol. Chem. 287:24649-24661(2012).
RN [5] {ECO:0007744|PDB:4Y6N, ECO:0007744|PDB:4Y6U, ECO:0007744|PDB:4Y7F, ECO:0007744|PDB:4Y7G, ECO:0007744|PDB:4Y9X}
RP X-RAY CRYSTALLOGRAPHY (2.27 ANGSTROMS) IN COMPLEXES WITH
RP 3-PHOSPHO-D-GLYCERATE; GLYCEROL-3-PHOSPHATE; UDP-ALPHA-D-GLUCOSE AND
RP MANGANESE ION, COFACTOR, SUBUNIT, AND REACTION MECHANISM.
RX PubMed=26136334; DOI=10.1002/anie.201504617;
RA Albesa-Jove D., Mendoza F., Rodrigo-Unzueta A., Gomollon-Bel F.,
RA Cifuente J.O., Urresti S., Comino N., Gomez H., Romero-Garcia J.,
RA Lluch J.M., Sancho-Vaello E., Biarnes X., Planas A., Merino P., Masgrau L.,
RA Guerin M.E.;
RT "A native ternary complex trapped in a crystal reveals the catalytic
RT mechanism of a retaining glycosyltransferase.";
RL Angew. Chem. Int. Ed. Engl. 54:9898-9902(2015).
RN [6] {ECO:0007744|PDB:5JQX, ECO:0007744|PDB:5JT0, ECO:0007744|PDB:5JUC}
RP X-RAY CRYSTALLOGRAPHY (2.82 ANGSTROMS) IN COMPLEXES WITH
RP 3-PHOSPHO-D-GLYCERATE; UDP; GLUCOSYL-3-PHOSPHOGLYCERATE AND MANGANESE ION,
RP AND COFACTOR.
RX PubMed=28625787; DOI=10.1016/j.str.2017.05.009;
RA Albesa-Jove D., Romero-Garcia J., Sancho-Vaello E., Contreras F.X.,
RA Rodrigo-Unzueta A., Comino N., Carreras-Gonzalez A., Arrasate P.,
RA Urresti S., Biarnes X., Planas A., Guerin M.E.;
RT "Structural snapshots and loop dynamics along the catalytic cycle of
RT glycosyltransferase GpgS.";
RL Structure 25:1034-1044(2017).
CC -!- FUNCTION: Involved in the biosynthesis of 6-O-methylglucose
CC lipopolysaccarides (MGLPs). Catalyzes the transfer of the glucose
CC moiety from UDP-alpha-D-glucose (UDP-Glc) to the position 2 of 3-
CC phospho-D-glycerate (3-PGA) to form glucosyl-3-phosphoglycerate (GPG).
CC {ECO:0000269|PubMed:22637481}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2R)-3-phosphoglycerate + an NDP-alpha-D-glucose = (2R)-2-O-
CC (alpha-D-glucopyranosyl)-3-phospho-glycerate + a ribonucleoside 5'-
CC diphosphate + H(+); Xref=Rhea:RHEA:47244, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57930, ChEBI:CHEBI:58272, ChEBI:CHEBI:62600,
CC ChEBI:CHEBI:76533; EC=2.4.1.266;
CC Evidence={ECO:0000269|PubMed:22637481};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47245;
CC Evidence={ECO:0000305|PubMed:22637481};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2R)-3-phosphoglycerate + UDP-alpha-D-glucose = (2R)-2-O-
CC (alpha-D-glucopyranosyl)-3-phospho-glycerate + H(+) + UDP;
CC Xref=Rhea:RHEA:31319, ChEBI:CHEBI:15378, ChEBI:CHEBI:58223,
CC ChEBI:CHEBI:58272, ChEBI:CHEBI:58885, ChEBI:CHEBI:62600;
CC EC=2.4.1.266; Evidence={ECO:0000269|PubMed:22637481};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31320;
CC Evidence={ECO:0000305|PubMed:22637481};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:22637481};
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000269|PubMed:22637481};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:22637481, ECO:0000305|PubMed:26136334,
CC ECO:0000305|PubMed:28625787};
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000269|PubMed:22637481};
CC Name=Co(2+); Xref=ChEBI:CHEBI:48828;
CC Evidence={ECO:0000269|PubMed:22637481};
CC Note=Requires divalent cations for activity. Mg(2+) gives the maximal
CC activity, but the enzyme can also use Ca(2+), Mn(2+), Fe(2+) or Co(2+)
CC ions, but not Zn(2+) or Cu(2+) ions. {ECO:0000269|PubMed:22637481};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:19015727,
CC ECO:0000269|PubMed:22637481, ECO:0000269|PubMed:26136334}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC {ECO:0000305|PubMed:19099550}.
CC -!- MISCELLANEOUS: The glucosyltransferase GpgS does not possess a putative
CC nucleophile residue that could result in the formation of a glycosyl-
CC enzyme covalent intermediate. Therefore, it is expected that the
CC reaction would proceed through a front-side substrate-assisted SNi-type
CC mechanism where the breaking of the glucosidic bond is stabilized by
CC the interaction of the acceptor hydrogen atom O3 of the acceptor 3-PGA
CC with the beta-phosphate of the nucleotide sugar.
CC {ECO:0000269|PubMed:26136334}.
CC -!- SIMILARITY: Belongs to the glycosyltransferase 2 family. {ECO:0000305}.
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DR EMBL; AL123456; CCP43964.1; -; Genomic_DNA.
DR PIR; F70609; F70609.
DR RefSeq; NP_215724.1; NC_000962.3.
DR RefSeq; WP_003406242.1; NZ_NVQJ01000039.1.
DR PDB; 3E25; X-ray; 2.70 A; A=1-324.
DR PDB; 3E26; X-ray; 2.50 A; A=1-324.
DR PDB; 4DDZ; X-ray; 2.60 A; A=1-324.
DR PDB; 4DE7; X-ray; 3.00 A; A=1-324.
DR PDB; 4DEC; X-ray; 1.98 A; A=1-324.
DR PDB; 4Y6N; X-ray; 2.35 A; A=1-324.
DR PDB; 4Y6U; X-ray; 2.27 A; A=1-324.
DR PDB; 4Y7F; X-ray; 3.23 A; A=1-324.
DR PDB; 4Y7G; X-ray; 2.59 A; A=1-324.
DR PDB; 4Y9X; X-ray; 2.64 A; A=1-324.
DR PDB; 5JQQ; X-ray; 2.60 A; A=1-324.
DR PDB; 5JQX; X-ray; 2.82 A; A/B/C/D=1-324.
DR PDB; 5JT0; X-ray; 2.80 A; A=1-324.
DR PDB; 5JUC; X-ray; 2.80 A; A=1-324.
DR PDBsum; 3E25; -.
DR PDBsum; 3E26; -.
DR PDBsum; 4DDZ; -.
DR PDBsum; 4DE7; -.
DR PDBsum; 4DEC; -.
DR PDBsum; 4Y6N; -.
DR PDBsum; 4Y6U; -.
DR PDBsum; 4Y7F; -.
DR PDBsum; 4Y7G; -.
DR PDBsum; 4Y9X; -.
DR PDBsum; 5JQQ; -.
DR PDBsum; 5JQX; -.
DR PDBsum; 5JT0; -.
DR PDBsum; 5JUC; -.
DR AlphaFoldDB; P9WMW9; -.
DR SMR; P9WMW9; -.
DR STRING; 83332.Rv1208; -.
DR PaxDb; P9WMW9; -.
DR DNASU; 886085; -.
DR GeneID; 45425178; -.
DR GeneID; 886085; -.
DR KEGG; mtu:Rv1208; -.
DR TubercuList; Rv1208; -.
DR eggNOG; COG0463; Bacteria.
DR OMA; HLVKSFY; -.
DR PhylomeDB; P9WMW9; -.
DR BRENDA; 2.4.1.266; 3445.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0016758; F:hexosyltransferase activity; IDA:MTBBASE.
DR GO; GO:0000287; F:magnesium ion binding; IDA:MTBBASE.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:MTBBASE.
DR GO; GO:0006011; P:UDP-glucose metabolic process; IDA:MTBBASE.
DR Gene3D; 3.90.550.10; -; 1.
DR InterPro; IPR001173; Glyco_trans_2-like.
DR InterPro; IPR029044; Nucleotide-diphossugar_trans.
DR Pfam; PF00535; Glycos_transf_2; 1.
DR SUPFAM; SSF53448; SSF53448; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium; Cobalt; Glycosyltransferase; Iron; Magnesium;
KW Manganese; Metal-binding; Reference proteome; Transferase.
FT CHAIN 1..324
FT /note="Glucosyl-3-phosphoglycerate synthase"
FT /id="PRO_0000420163"
FT BINDING 50..54
FT /ligand="UDP-alpha-D-glucose"
FT /ligand_id="ChEBI:CHEBI:58885"
FT /evidence="ECO:0000269|PubMed:26136334,
FT ECO:0007744|PDB:4Y6N, ECO:0007744|PDB:4Y6U,
FT ECO:0007744|PDB:4Y7F, ECO:0007744|PDB:4Y7G,
FT ECO:0007744|PDB:4Y9X"
FT BINDING 81
FT /ligand="UDP-alpha-D-glucose"
FT /ligand_id="ChEBI:CHEBI:58885"
FT /evidence="ECO:0000269|PubMed:26136334,
FT ECO:0007744|PDB:4Y6N, ECO:0007744|PDB:4Y6U,
FT ECO:0007744|PDB:4Y7F, ECO:0007744|PDB:4Y7G,
FT ECO:0007744|PDB:4Y9X"
FT BINDING 114
FT /ligand="(2R)-2-O-(alpha-D-glucopyranosyl)-3-phospho-
FT glycerate"
FT /ligand_id="ChEBI:CHEBI:62600"
FT /evidence="ECO:0000269|PubMed:28625787,
FT ECO:0007744|PDB:5JT0"
FT BINDING 114
FT /ligand="UDP-alpha-D-glucose"
FT /ligand_id="ChEBI:CHEBI:58885"
FT /evidence="ECO:0000269|PubMed:26136334,
FT ECO:0007744|PDB:4Y6N, ECO:0007744|PDB:4Y6U,
FT ECO:0007744|PDB:4Y7F, ECO:0007744|PDB:4Y7G,
FT ECO:0007744|PDB:4Y9X"
FT BINDING 134..135
FT /ligand="UDP-alpha-D-glucose"
FT /ligand_id="ChEBI:CHEBI:58885"
FT /evidence="ECO:0000269|PubMed:26136334,
FT ECO:0007744|PDB:4Y6N, ECO:0007744|PDB:4Y6U,
FT ECO:0007744|PDB:4Y7F, ECO:0007744|PDB:4Y7G,
FT ECO:0007744|PDB:4Y9X"
FT BINDING 136
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000269|PubMed:26136334,
FT ECO:0007744|PDB:4Y6N, ECO:0007744|PDB:4Y6U,
FT ECO:0007744|PDB:4Y7F, ECO:0007744|PDB:4Y7G,
FT ECO:0007744|PDB:4Y9X"
FT BINDING 184..187
FT /ligand="(2R)-2-O-(alpha-D-glucopyranosyl)-3-phospho-
FT glycerate"
FT /ligand_id="ChEBI:CHEBI:62600"
FT /evidence="ECO:0000269|PubMed:28625787,
FT ECO:0007744|PDB:5JT0"
FT BINDING 184..187
FT /ligand="(2R)-3-phosphoglycerate"
FT /ligand_id="ChEBI:CHEBI:58272"
FT /evidence="ECO:0000269|PubMed:26136334,
FT ECO:0000269|PubMed:28625787, ECO:0007744|PDB:4Y6N,
FT ECO:0007744|PDB:4Y6U, ECO:0007744|PDB:4Y9X,
FT ECO:0007744|PDB:5JQX"
FT BINDING 229..232
FT /ligand="UDP-alpha-D-glucose"
FT /ligand_id="ChEBI:CHEBI:58885"
FT /evidence="ECO:0000269|PubMed:26136334,
FT ECO:0007744|PDB:4Y6N, ECO:0007744|PDB:4Y6U,
FT ECO:0007744|PDB:4Y7F, ECO:0007744|PDB:4Y7G,
FT ECO:0007744|PDB:4Y9X"
FT BINDING 256..261
FT /ligand="UDP-alpha-D-glucose"
FT /ligand_id="ChEBI:CHEBI:58885"
FT /evidence="ECO:0000269|PubMed:26136334,
FT ECO:0007744|PDB:4Y6N, ECO:0007744|PDB:4Y6U,
FT ECO:0007744|PDB:4Y7F, ECO:0007744|PDB:4Y7G,
FT ECO:0007744|PDB:4Y9X"
FT BINDING 256
FT /ligand="(2R)-2-O-(alpha-D-glucopyranosyl)-3-phospho-
FT glycerate"
FT /ligand_id="ChEBI:CHEBI:62600"
FT /evidence="ECO:0000269|PubMed:28625787,
FT ECO:0007744|PDB:5JT0"
FT BINDING 258
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000269|PubMed:26136334,
FT ECO:0007744|PDB:4Y6N, ECO:0007744|PDB:4Y6U,
FT ECO:0007744|PDB:4Y7F, ECO:0007744|PDB:4Y7G,
FT ECO:0007744|PDB:4Y9X"
FT BINDING 260
FT /ligand="(2R)-3-phosphoglycerate"
FT /ligand_id="ChEBI:CHEBI:58272"
FT /evidence="ECO:0000269|PubMed:26136334,
FT ECO:0007744|PDB:4Y6N, ECO:0007744|PDB:4Y6U"
FT STRAND 21..25
FT /evidence="ECO:0007829|PDB:4DEC"
FT HELIX 33..40
FT /evidence="ECO:0007829|PDB:4DEC"
FT STRAND 45..53
FT /evidence="ECO:0007829|PDB:4DEC"
FT TURN 55..57
FT /evidence="ECO:0007829|PDB:4DEC"
FT HELIX 58..65
FT /evidence="ECO:0007829|PDB:4DEC"
FT HELIX 66..68
FT /evidence="ECO:0007829|PDB:4DEC"
FT TURN 70..72
FT /evidence="ECO:0007829|PDB:4DEC"
FT STRAND 73..80
FT /evidence="ECO:0007829|PDB:4DEC"
FT HELIX 87..93
FT /evidence="ECO:0007829|PDB:4DEC"
FT STRAND 97..100
FT /evidence="ECO:0007829|PDB:4DEC"
FT HELIX 101..104
FT /evidence="ECO:0007829|PDB:4DEC"
FT HELIX 114..123
FT /evidence="ECO:0007829|PDB:4DEC"
FT STRAND 128..132
FT /evidence="ECO:0007829|PDB:4DEC"
FT STRAND 137..139
FT /evidence="ECO:0007829|PDB:4DEC"
FT HELIX 144..154
FT /evidence="ECO:0007829|PDB:4DEC"
FT STRAND 155..157
FT /evidence="ECO:0007829|PDB:4DEC"
FT STRAND 160..166
FT /evidence="ECO:0007829|PDB:4DEC"
FT HELIX 185..189
FT /evidence="ECO:0007829|PDB:4DEC"
FT HELIX 191..198
FT /evidence="ECO:0007829|PDB:4DEC"
FT HELIX 200..204
FT /evidence="ECO:0007829|PDB:4DEC"
FT STRAND 213..216
FT /evidence="ECO:0007829|PDB:4DEC"
FT HELIX 217..220
FT /evidence="ECO:0007829|PDB:4DEC"
FT HELIX 228..230
FT /evidence="ECO:0007829|PDB:4DEC"
FT HELIX 231..243
FT /evidence="ECO:0007829|PDB:4DEC"
FT HELIX 245..247
FT /evidence="ECO:0007829|PDB:4DEC"
FT STRAND 248..255
FT /evidence="ECO:0007829|PDB:4DEC"
FT HELIX 263..280
FT /evidence="ECO:0007829|PDB:4DEC"
FT STRAND 291..295
FT /evidence="ECO:0007829|PDB:4DEC"
FT STRAND 303..307
FT /evidence="ECO:0007829|PDB:4DEC"
FT HELIX 318..321
FT /evidence="ECO:0007829|PDB:4DEC"
SQ SEQUENCE 324 AA; 34379 MW; 7CE4AE274C1A23BA CRC64;
MTASELVAGD LAGGRAPGAL PLDTTWHRPG WTIGELEAAK AGRTISVVLP ALNEEATIES
VIDSISPLVD GLVDELIVLD SGSTDDTEIR AIASGARVVS REQALPEVPV RPGKGEALWR
SLAATSGDIV VFIDSDLINP HPLFVPWLVG PLLTGEGIQL VKSFYRRPLQ VSDVTSGVCA
TGGGRVTELV ARPLLAALRP ELGCVLQPLS GEYAASRELL TSLPFAPGYG VEIGLLIDTF
DRLGLDAIAQ VNLGVRAHRN RPLDELGAMS RQVIATLLSR CGIPDSGVGL TQFLPGGPDD
SDYTRHTWPV SLVDRPPMKV MRPR
