1PN3

Crystal Structure of TDP-epi-Vancosaminyltransferase GtfA in complexes with TDP and the acceptor substrate DVV.

Summary for 1PN3

• Entry DOI: 10.2210/pdb1pn3/pdb
• Related: 1AA5 1C0Q 1C0R 1FVM 1GAC 1GHG 1PNV 1QD8 1RRV 1SHO
• Related PRD ID: PRD_000205
• Descriptor: GLYCOSYLTRANSFERASE GTFA, DESVANCOSAMINYL VANCOMYCIN, THYMIDINE-5'-DIPHOSPHATE, ... (5 entities in total)
• Functional Keywords: gt-b glycosyltransferase, rossmann fold, glycopeptide, vancomycin, antibiotic, transferase-antibiotic complex, transferase/antibiotic
• Biological source: AMYCOLATOPSIS ORIENTALIS; More
• Total number of polymer chains: 4
• Total formula weight: 88609.25

Authors

Mulichak, A.M.,Losey, H.C.,Lu, W.,Wawrzak, Z.,Walsh, C.T.,Garavito, R.M. (deposition date: 2003-06-12, release date: 2003-08-12, Last modification date: 2020-07-29)

Primary citation

Mulichak, A.M.,Losey, H.C.,Lu, W.,Wawrzak, Z.,Walsh, C.T.,Garavito, R.M.
Structure of the Tdp-Epi-Vancosaminyltransferase Gtfa from the Chloroeremomycin Biosynthetic Pathway.
Proc.Natl.Acad.Sci.USA, 100:9238-, 2003

PubMed Abstract: 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.

PubMed: 12874381
DOI: 10.1073/PNAS.1233577100

Experimental method

X-RAY DIFFRACTION (2.8 Å)