| Structural highlights
1pnv is a 3 chain structure with sequence from Amycolatopsis orientalis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2.8Å |
| Ligands: | , , , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
GTFA_AMYOR Catalyzes the attachment of 4-epi-vancosamine from a TDP donor to the beta-OH-Tyr-6 of the aglycone cosubstrate in the biosynthesis of glycopeptide antibiotic chloroeremomycin, a member of the vancomycin group of antibiotics. Strongly prefers devancoaminyl-vancomycin (DVV) as substrate rather than the heptapeptide vancomycin aglycone (AGV). Acts downstream of GtfB.[1] [2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
During the biosynthesis of the vancomycin-class antibiotic chloroeremomycin, TDP-epi-vancosaminyltransferase GtfA catalyzes the attachment of 4-epi-vancosamine from a TDP donor to the beta-OHTyr-6 of the aglycone cosubstrate. Glycosyltransferases from this pathway are potential tools for the combinatorial design of new antibiotics that are effective against vancomycin-resistant bacterial strains. These enzymes are members of the GT-B glycosyltransferase superfamily, which share a homologous bidomain topology. We present the 2.8-A crystal structures of GtfA complexes with vancomycin and the natural monoglycosylated peptide substrate, representing the first direct observation of acceptor substrate binding among closely related glycosyltransferases. The acceptor substrates bind to the N-terminal domain such that the aglycone substrate's reactive hydroxyl group hydrogen bonds to the side chains of Ser-10 and Asp-13, thus identifying these as residues of potential catalytic importance. As well as an open form of the enzyme, the crystal structures have revealed a closed form in which a TDP ligand is bound at a donor substrate site in the interdomain cleft, thereby illustrating not only binding interactions, but the conformational changes in the enzyme that accompany substrate binding.
Structure of the TDP-epi-vancosaminyltransferase GtfA from the chloroeremomycin biosynthetic pathway.,Mulichak AM, Losey HC, Lu W, Wawrzak Z, Walsh CT, Garavito RM Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9238-43. Epub 2003 Jul 21. PMID:12874381[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Lu W, Oberthür M, Leimkuhler C, Tao J, Kahne D, Walsh CT. Characterization of a regiospecific epivancosaminyl transferase GtfA and enzymatic reconstitution of the antibiotic chloroeremomycin. Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4390-5. PMID:15070728 doi:10.1073/pnas.0400277101
- ↑ Truman AW, Dias MV, Wu S, Blundell TL, Huang F, Spencer JB. Chimeric glycosyltransferases for the generation of hybrid glycopeptides. Chem Biol. 2009 Jun 26;16(6):676-85. PMID:19549605 doi:S1074-5521(09)00178-1
- ↑ Solenberg PJ, Matsushima P, Stack DR, Wilkie SC, Thompson RC, Baltz RH. Production of hybrid glycopeptide antibiotics in vitro and in Streptomyces toyocaensis. Chem Biol. 1997 Mar;4(3):195-202. PMID:9115410 doi:10.1016/s1074-5521(97)90288-x
- ↑ Mulichak AM, Losey HC, Lu W, Wawrzak Z, Walsh CT, Garavito RM. Structure of the TDP-epi-vancosaminyltransferase GtfA from the chloroeremomycin biosynthetic pathway. Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9238-43. Epub 2003 Jul 21. PMID:12874381 doi:10.1073/pnas.1233577100
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