GTFA_AMYOR
ID GTFA_AMYOR Reviewed; 396 AA.
AC P96558;
DT 01-OCT-2014, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 92.
DE RecName: Full=dTDP-epi-vancosaminyltransferase;
DE EC=2.4.1.311;
DE AltName: Full=Glycosyltransferase AH1;
DE Short=GtfAH1;
DE AltName: Full=Glycosyltransferase GtfA;
GN Name=gtfA;
OS Amycolatopsis orientalis (Nocardia orientalis).
OC Bacteria; Actinobacteria; Pseudonocardiales; Pseudonocardiaceae;
OC Amycolatopsis.
OX NCBI_TaxID=31958;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RX PubMed=9115410; DOI=10.1016/s1074-5521(97)90288-x;
RA Solenberg P.J., Matsushima P., Stack D.R., Wilkie S.C., Thompson R.C.,
RA Baltz R.H.;
RT "Production of hybrid glycopeptide antibiotics in vitro and in Streptomyces
RT toyocaensis.";
RL Chem. Biol. 4:195-202(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND PATHWAY.
RX PubMed=9545426; DOI=10.1016/s1074-5521(98)90060-6;
RA van Wageningen A., Kirkpatrick P., Williams D., Harris B., Kershaw J.,
RA Lennard N., Jones M., Jones S., Solenberg P.;
RT "Sequencing and analysis of genes involved in the biosynthesis of a
RT vancomycin group antibiotic.";
RL Chem. Biol. 5:155-162(1998).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=15070728; DOI=10.1073/pnas.0400277101;
RA Lu W., Oberthuer M., Leimkuhler C., Tao J., Kahne D., Walsh C.T.;
RT "Characterization of a regiospecific epivancosaminyl transferase GtfA and
RT enzymatic reconstitution of the antibiotic chloroeremomycin.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:4390-4395(2004).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) IN COMPLEX WITH VANCOMYCIN AND
RP DTDP-BETA-L-4-EPI-VANCOSAMINE.
RX PubMed=12874381; DOI=10.1073/pnas.1233577100;
RA Mulichak A.M., Losey H.C., Lu W., Wawrzak Z., Walsh C.T., Garavito R.M.;
RT "Structure of the TDP-epi-vancosaminyltransferase GtfA from the
RT chloroeremomycin biosynthetic pathway.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:9238-9243(2003).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (1.15 ANGSTROMS) OF 1-214 IN COMPLEX WITH
RP UDP-2-DEOXY-2-FLUORO-GLUCOSE, AND FUNCTION.
RX PubMed=19549605; DOI=10.1016/j.chembiol.2009.04.013;
RA Truman A.W., Dias M.V., Wu S., Blundell T.L., Huang F., Spencer J.B.;
RT "Chimeric glycosyltransferases for the generation of hybrid
RT glycopeptides.";
RL Chem. Biol. 16:676-685(2009).
CC -!- FUNCTION: Catalyzes the attachment of 4-epi-vancosamine from a TDP
CC donor to the beta-OH-Tyr-6 of the aglycone cosubstrate in the
CC biosynthesis of glycopeptide antibiotic chloroeremomycin, a member of
CC the vancomycin group of antibiotics. Strongly prefers devancoaminyl-
CC vancomycin (DVV) as substrate rather than the heptapeptide vancomycin
CC aglycone (AGV). Acts downstream of GtfB. {ECO:0000269|PubMed:15070728,
CC ECO:0000269|PubMed:19549605, ECO:0000269|PubMed:9115410}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=devancoaminyl-vancomycin + dTDP-beta-L-4-epi-vancosamine =
CC chloroorienticin B + dTDP + H(+); Xref=Rhea:RHEA:38591,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:58369, ChEBI:CHEBI:75953,
CC ChEBI:CHEBI:75957, ChEBI:CHEBI:75963; EC=2.4.1.311;
CC Evidence={ECO:0000269|PubMed:15070728};
CC -!- PATHWAY: Antibiotic biosynthesis; vancomycin biosynthesis.
CC {ECO:0000269|PubMed:15070728, ECO:0000269|PubMed:9545426}.
CC -!- MISCELLANEOUS: In A.orientalis different glycosyltransferases are
CC involved in biosynthesis of the vancomycin group of antibiotics. GtfA,
CC GtfB (AC P96559) and GtfC (AC P96560) are involved in biosynthesis of
CC antibiotic chloroeremomycin, while GtfD (AC Q9AFC7) and GtfE (AC
CC G4V4R9) are involved in biosynthesis of vancomycin.
CC -!- SIMILARITY: Belongs to the glycosyltransferase 28 family.
CC {ECO:0000305}.
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DR EMBL; U84349; AAB49292.1; -; Genomic_DNA.
DR EMBL; AJ223998; CAA11774.1; -; Genomic_DNA.
DR PIR; T30584; T30584.
DR PDB; 1PN3; X-ray; 2.80 A; A/B=1-396.
DR PDB; 1PNV; X-ray; 2.80 A; A/B=1-396.
DR PDB; 3H4I; X-ray; 1.30 A; A=1-214.
DR PDB; 3H4T; X-ray; 1.15 A; A=1-214.
DR PDBsum; 1PN3; -.
DR PDBsum; 1PNV; -.
DR PDBsum; 3H4I; -.
DR PDBsum; 3H4T; -.
DR AlphaFoldDB; P96558; -.
DR SMR; P96558; -.
DR DrugBank; DB04529; Desvancosaminyl vancomycin.
DR CAZy; GT1; Glycosyltransferase Family 1.
DR KEGG; ag:CAA11774; -.
DR BRENDA; 2.4.1.311; 315.
DR UniPathway; UPA00162; -.
DR EvolutionaryTrace; P96558; -.
DR GO; GO:0016758; F:hexosyltransferase activity; IDA:UniProtKB.
DR GO; GO:0008194; F:UDP-glycosyltransferase activity; IEA:InterPro.
DR GO; GO:0005975; P:carbohydrate metabolic process; IEA:InterPro.
DR GO; GO:0030259; P:lipid glycosylation; IEA:InterPro.
DR GO; GO:0033072; P:vancomycin biosynthetic process; IDA:UniProtKB.
DR CDD; cd03784; GT1_Gtf-like; 1.
DR InterPro; IPR004276; GlycoTrans_28_N.
DR InterPro; IPR002213; UDP_glucos_trans.
DR Pfam; PF03033; Glyco_transf_28; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antibiotic biosynthesis; Glycosyltransferase; Transferase.
FT CHAIN 1..396
FT /note="dTDP-epi-vancosaminyltransferase"
FT /id="PRO_0000430436"
FT BINDING 10..12
FT /ligand="dTDP-beta-L-4-epi-vancosamine"
FT /ligand_id="ChEBI:CHEBI:75957"
FT /evidence="ECO:0000305|PubMed:12874381"
FT BINDING 127
FT /ligand="devancoaminyl-vancomycin"
FT /ligand_id="ChEBI:CHEBI:75953"
FT /evidence="ECO:0000305|PubMed:12874381"
FT BINDING 133
FT /ligand="devancoaminyl-vancomycin"
FT /ligand_id="ChEBI:CHEBI:75953"
FT /evidence="ECO:0000305|PubMed:12874381"
FT BINDING 141
FT /ligand="devancoaminyl-vancomycin"
FT /ligand_id="ChEBI:CHEBI:75953"
FT /evidence="ECO:0000305|PubMed:12874381"
FT BINDING 169
FT /ligand="devancoaminyl-vancomycin"
FT /ligand_id="ChEBI:CHEBI:75953"
FT /evidence="ECO:0000305|PubMed:12874381"
FT BINDING 207
FT /ligand="dTDP-beta-L-4-epi-vancosamine"
FT /ligand_id="ChEBI:CHEBI:75957"
FT /evidence="ECO:0000305|PubMed:12874381"
FT BINDING 230
FT /ligand="dTDP-beta-L-4-epi-vancosamine"
FT /ligand_id="ChEBI:CHEBI:75957"
FT /evidence="ECO:0000305|PubMed:12874381"
FT BINDING 277..278
FT /ligand="dTDP-beta-L-4-epi-vancosamine"
FT /ligand_id="ChEBI:CHEBI:75957"
FT /evidence="ECO:0000305|PubMed:12874381"
FT BINDING 293..298
FT /ligand="dTDP-beta-L-4-epi-vancosamine"
FT /ligand_id="ChEBI:CHEBI:75957"
FT /evidence="ECO:0000305|PubMed:12874381"
FT STRAND 3..10
FT /evidence="ECO:0007829|PDB:3H4T"
FT HELIX 11..26
FT /evidence="ECO:0007829|PDB:3H4T"
FT STRAND 31..35
FT /evidence="ECO:0007829|PDB:3H4T"
FT HELIX 37..39
FT /evidence="ECO:0007829|PDB:3H4T"
FT HELIX 40..45
FT /evidence="ECO:0007829|PDB:3H4T"
FT STRAND 50..52
FT /evidence="ECO:0007829|PDB:3H4T"
FT HELIX 59..61
FT /evidence="ECO:0007829|PDB:3H4T"
FT HELIX 72..74
FT /evidence="ECO:0007829|PDB:3H4T"
FT HELIX 75..90
FT /evidence="ECO:0007829|PDB:3H4T"
FT STRAND 94..100
FT /evidence="ECO:0007829|PDB:3H4T"
FT HELIX 102..115
FT /evidence="ECO:0007829|PDB:3H4T"
FT STRAND 119..125
FT /evidence="ECO:0007829|PDB:3H4T"
FT HELIX 126..128
FT /evidence="ECO:0007829|PDB:3H4T"
FT HELIX 130..132
FT /evidence="ECO:0007829|PDB:3H4T"
FT HELIX 135..159
FT /evidence="ECO:0007829|PDB:3H4T"
FT HELIX 168..173
FT /evidence="ECO:0007829|PDB:3H4T"
FT TURN 183..185
FT /evidence="ECO:0007829|PDB:3H4T"
FT STRAND 193..197
FT /evidence="ECO:0007829|PDB:1PNV"
FT HELIX 211..216
FT /evidence="ECO:0007829|PDB:1PN3"
FT STRAND 219..221
FT /evidence="ECO:0007829|PDB:1PN3"
FT STRAND 224..227
FT /evidence="ECO:0007829|PDB:1PN3"
FT HELIX 235..249
FT /evidence="ECO:0007829|PDB:1PN3"
FT STRAND 254..257
FT /evidence="ECO:0007829|PDB:1PN3"
FT TURN 259..262
FT /evidence="ECO:0007829|PDB:1PN3"
FT STRAND 274..277
FT /evidence="ECO:0007829|PDB:1PN3"
FT HELIX 280..284
FT /evidence="ECO:0007829|PDB:1PN3"
FT STRAND 290..294
FT /evidence="ECO:0007829|PDB:1PN3"
FT HELIX 296..305
FT /evidence="ECO:0007829|PDB:1PN3"
FT STRAND 309..312
FT /evidence="ECO:0007829|PDB:1PN3"
FT HELIX 324..331
FT /evidence="ECO:0007829|PDB:1PN3"
FT STRAND 334..338
FT /evidence="ECO:0007829|PDB:1PN3"
FT HELIX 345..355
FT /evidence="ECO:0007829|PDB:1PN3"
FT HELIX 360..367
FT /evidence="ECO:0007829|PDB:1PN3"
FT HELIX 368..370
FT /evidence="ECO:0007829|PDB:1PN3"
FT HELIX 375..390
FT /evidence="ECO:0007829|PDB:1PN3"
SQ SEQUENCE 396 AA; 41662 MW; A771471559C6CBF5 CRC64;
MRVLITGCGS RGDTEPLVAL AARLRELGAD ARMCLPPDYV ERCAEVGVPM VPVGRAVRAG
AREPGELPPG AAEVVTEVVA EWFDKVPAAI EGCDAVVTTG LLPAAVAVRS MAEKLGIPYR
YTVLSPDHLP SEQSQAERDM YNQGADRLFG DAVNSHRASI GLPPVEHLYD YGYTDQPWLA
ADPVLSPLRP TDLGTVQTGA WILPDERPLS AELEAFLAAG STPVYVGFGS SSRPATADAA
KMAIKAVRAS GRRIVLSRGW ADLVLPDDGA DCFVVGEVNL QELFGRVAAA IHHDSAGTTL
LAMRAGIPQI VVRRVVDNVV EQAYHADRVA ELGVGVAVDG PVPTIDSLSA ALDTALAPEI
RARATTVADT IRADGTTVAA QLLFDAVSLE KPTVPA
