1iir

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spinqualitylabelsall models 1iir, resolution 1.8Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal Structure of UDP-glucosyltransferase GtfB

Overview

BACKGROUND: Members of the vancomycin group of glycopeptide antibiotics, have an oxidatively crosslinked heptapeptide scaffold decorated at the, hydroxyl groups of 4-OH-Phegly4 or beta-OH-Tyr6 with mono- (residue 6) or, disaccharides (residue 4). The disaccharide in vancomycin itself is, L-vancosamine-1,2-glucose, and in chloroeremomycin it is, L-4-epi-vancosamine-1,2-glucose. The sugars and their substituents play an, important role in efficacy, particularly against vancomycin-resistant, pathogenic enterococci. RESULTS: The glucosyltransferase, GtfB, that, transfers the glucose residue from UDP-glucose to the 4-OH-Phegly4 residue, of the vancomycin aglycone, initiating the glycosylation pathway in, chloroeremomycin maturation, has been crystallized, and its structure has, been determined by X-ray analysis at 1.8 A resolution. The enzyme has a, two-domain structure, with a deep interdomain cleft identified as the, likely site of UDP-glucose binding. A hydrophobic patch on the surface of, the N-terminal domain is proposed to be the binding site of the aglycone, substrate. Mutagenesis has revealed Asp332 as the best candidate for the, general base in the glucosyltransfer reaction. CONCLUSIONS: The structure, of GtfB places it in a growing group of glycosyltransferases, including, Escherichia coli MurG and a beta-glucosyltransferase from T4 phage, which, together form a subclass of the glycosyltransferase superfamily and give, insights into the recognition of the NDP-sugar and aglycone cosubstrates., A single major interdomain linker between the N- and C- terminal domains, suggests that reprogramming of sugar transfer or aglycone recognition in, the antibiotic glycosyltransferases, including the glycopeptide and also, the macrolide antibiotics, will be facilitated by this structural, information.

About this Structure

1IIR is a Single protein structure of sequence from Amycolatopsis orientalis with SO4 and MG as ligands. Full crystallographic information is available from OCA.

Reference

Structure of the UDP-glucosyltransferase GtfB that modifies the heptapeptide aglycone in the biosynthesis of vancomycin group antibiotics., Mulichak AM, Losey HC, Walsh CT, Garavito RM, Structure. 2001 Jul 3;9(7):547-57. PMID:11470430

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