Abstract
MurG is an essential bacterial glycosyltransferase enzyme in Pseudomonas aeruginosa performing one of the key membrane steps of peptidoglycan synthesis catalyzing the transfer of N-acetyl glucosamine (GlcNAc) from its donor substrate, UDP-GlcNAc, to the acceptor substrate Lipid I. We have solved the crystal structure of the complex between Pseudomonas aeruginosa MurG and UDP-GlcNAc and compared it with the previously solved complex from E. coli. The structure reveals a large-scale conformational change in the relative orientations of the N- and C-terminal domains, which has the effect of widening the cofactor binding site and displacing the UDP-GlcNAc donor. These results suggest new opportunities to design potent inhibitors of peptidoglycan biosynthesis.
Keywords: Transferase, peptidoglycan biosynthesis, X-ray crystallography, fluorimetry, enzymology.
Protein & Peptide Letters
Title:Crystal Structure of the Pseudomonas aeruginosa MurG: UDP-GlcNAc Substrate Complex
Volume: 20 Issue: 9
Author(s): Kieron Brown, Sarah C.M. Vial, Neesha Dedi, James Westcott, Stephen Scally, Timothy D.H. Bugg, Peter A. Charlton and Graham M.T. Cheetham
Affiliation:
Keywords: Transferase, peptidoglycan biosynthesis, X-ray crystallography, fluorimetry, enzymology.
Abstract: MurG is an essential bacterial glycosyltransferase enzyme in Pseudomonas aeruginosa performing one of the key membrane steps of peptidoglycan synthesis catalyzing the transfer of N-acetyl glucosamine (GlcNAc) from its donor substrate, UDP-GlcNAc, to the acceptor substrate Lipid I. We have solved the crystal structure of the complex between Pseudomonas aeruginosa MurG and UDP-GlcNAc and compared it with the previously solved complex from E. coli. The structure reveals a large-scale conformational change in the relative orientations of the N- and C-terminal domains, which has the effect of widening the cofactor binding site and displacing the UDP-GlcNAc donor. These results suggest new opportunities to design potent inhibitors of peptidoglycan biosynthesis.
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Cite this article as:
Brown Kieron, Vial C.M. Sarah, Dedi Neesha, Westcott James, Scally Stephen, Bugg D.H. Timothy, Charlton A. Peter and Cheetham M.T. Graham, Crystal Structure of the Pseudomonas aeruginosa MurG: UDP-GlcNAc Substrate Complex, Protein & Peptide Letters 2013; 20 (9) . https://dx.doi.org/10.2174/0929866511320090006
DOI https://dx.doi.org/10.2174/0929866511320090006 |
Print ISSN 0929-8665 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5305 |
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