Crystal structure of the Pseudomonas aeruginosa MurG: UDP-GlcNAc substrate complex

Kieron Brown, Sarah C M Vial, Neesha Dedi, James Westcott, Stephen Scally, Timothy D H Bugg, Peter A Charlton, Graham M T Cheetham

Research output: Contribution to journalArticleResearchpeer-review

11 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)1002 - 1008
Number of pages7
JournalProtein and Peptide Letters
Volume20
Issue number9
DOIs
Publication statusPublished - 2013

Cite this