1pn3
From Proteopedia
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'''Crystal Structure of TDP-epi-Vancosaminyltransferase GtfA in complexes with TDP and the acceptor substrate DVV.''' | '''Crystal Structure of TDP-epi-Vancosaminyltransferase GtfA in complexes with TDP and the acceptor substrate DVV.''' | ||
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[[Category: Walsh, C T.]] | [[Category: Walsh, C T.]] | ||
[[Category: Wawrzak, Z.]] | [[Category: Wawrzak, Z.]] | ||
| - | [[Category: | + | [[Category: Gt-b glycosyltransferase]] |
| - | [[Category: | + | [[Category: Rossmann fold]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 05:16:03 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 02:16, 3 May 2008
Crystal Structure of TDP-epi-Vancosaminyltransferase GtfA in complexes with TDP and the acceptor substrate DVV.
Overview
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.
About this Structure
1PN3 is a Single protein structure of sequence from Amycolatopsis orientalis. Full crystallographic information is available from OCA.
Reference
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 Page seeded by OCA on Sat May 3 05:16:03 2008
