Protein and Peptide Letters · 2013 · 26 citations · 0 references
Life SciencesBiochemistryMolecular BiologyDrug DesignEnzymologyStructural BiologyGlycan BiosynthesisGlycan StructureMacromolecular AssemblyMicrobial GlycobiologyN-linked GlycosylationProtein GlycosylationBacterial Cell Wall BiosynthesisBacterial Glycan BiosynthesisBacterial Peptidoglycan SynthesisCrystal Structure RefinementGlycosyltransferase FunctionPeptidoglycan BiosynthesisPeptidoglycan GlycosylationPeptidoglycan Structure
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.