title: Acceptor specificity and inhibition of the bacterial cell-wall glycosyltransferase MurG.
abstract: A continuous fluorescence coupled enzyme assay was developed to study the acceptor specificity of the glycosyltransferase MurG toward different lipid I analogues with various substituents replacing the undecaprenyl moiety. It was found that most lipid I analogues are accepted as substrates and, amongst these, the saturated C14 analogue exhibits the best activity. This substrate was used to evaluate the inhibition activity of such antibiotics as moenomycin, vancomycin, and two chlorobiphenyl vancomycin derivatives. A vancomycin derivative with a chlorobiphenyl moiety on the aglycon section was identified as a potent inhibitor of MurG.
authors.affiliation: Department of Chemistry and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Haitian
authors.initials: H
authors.lastname: Liu
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Ritter
authors.forename: Reiko
authors.initials: R
authors.lastname: Sadamoto
authors.forename: Pamela S
authors.initials: PS
authors.lastname: Sears
authors.forename: Min
authors.initials: M
authors.lastname: Wu
authors.forename: Chi-Huey
authors.initials: CH
authors.lastname: Wong
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001455:Bambermycins / Q000737:chemistry / Q000494:pharmacology; D002473:Cell Wall / Q000201:enzymology / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D004926:Escherichia coli / Q000201:enzymology; D020128:Inhibitory Concentration 50; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry; D009005:Monosaccharides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D017351:N-Acetylglucosaminyltransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D013379:Substrate Specificity; D014640:Vancomycin / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D001425:Bacterial Outer Membrane Proteins; D004791:Enzyme Inhibitors; D008055:Lipids; D009005:Monosaccharides; D009842:Oligopeptides; C438940:lipid I; D001455:Bambermycins; D014640:Vancomycin; D017351:N-Acetylglucosaminyltransferases; C064057:UDP-N-acetylglucosamine-N-acetylmuramyl-(pentapeptide)pyrophosphoryl-undecaprenol N-acetylglucosamine transferase