title: Crystal structure of the Pseudomonas aeruginosa MurG: UDP-GlcNAc substrate complex.
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.
authors.affiliation: Vertex Pharmaceuticals (Europe) Ltd, 88 Milton Park, Abingdon, Oxfordshire, OX14 4RY, UK. kieron_brown@vrtx.com
authors.forename: Kieron
authors.initials: K
authors.lastname: Brown
authors.forename: Sarah C M
authors.initials: SC
authors.lastname: Vial
authors.forename: Neesha
authors.initials: N
authors.lastname: Dedi
authors.forename: James
authors.initials: J
authors.lastname: Westcott
authors.forename: Stephen
authors.initials: S
authors.lastname: Scally
authors.forename: Timothy D H
authors.initials: TD
authors.lastname: Bugg
authors.forename: Peter A
authors.initials: PA
authors.lastname: Charlton
authors.forename: Graham M T
authors.initials: GM
authors.lastname: Cheetham
mesh_terms: D000595:Amino Acid Sequence; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D003460:Crystallization; D018360:Crystallography, X-Ray; D005470:Fluorometry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017351:N-Acetylglucosaminyltransferases / Q000737:chemistry* / Q000378:metabolism; D010457:Peptidoglycan / Q000737:chemistry / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000201:enzymology; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D014537:Uridine Diphosphate N-Acetylglucosamine / Q000737:chemistry* / Q000378:metabolism
chemical_list: D001425:Bacterial Outer Membrane Proteins; D010457:Peptidoglycan; D011994:Recombinant Proteins; D014537:Uridine Diphosphate N-Acetylglucosamine; D017351:N-Acetylglucosaminyltransferases; C064057:UDP-N-acetylglucosamine-N-acetylmuramyl-(pentapeptide)pyrophosphoryl-undecaprenol N-acetylglucosamine transferase