Acceptor Specificity and Inhibition of the Bacterial Cell-Wall Glycosyltransferase MurG

• Published in: Chembiochem : a European journal of chemical biology 2003-07, Vol.4 (7), p.603-609
• Main Authors: Liu, Haitian, Ritter, Thomas K, Sadamoto, Reiko, Sears, Pamela S, Wu, Min, Wong, Chi-Huey
• Format: Article
• Language: English
• Subjects: Bacterial Outer Membrane Proteins - antagonists & inhibitors; Bacterial Outer Membrane Proteins - metabolism; Bambermycins - chemistry; Bambermycins - pharmacology; Cell Wall - enzymology; Cell Wall - metabolism; enzyme catalysis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - metabolism; Enzyme Inhibitors - pharmacology; Escherichia coli - enzymology; glycosyltransferases; inhibitors; Inhibitory Concentration 50; Lipid Metabolism; lipids; Lipids - chemistry; Monosaccharides - chemistry; Monosaccharides - metabolism; Monosaccharides - pharmacology; N-Acetylglucosaminyltransferases - antagonists & inhibitors; N-Acetylglucosaminyltransferases - metabolism; Oligopeptides - chemistry; Oligopeptides - metabolism; Oligopeptides - pharmacology; Substrate Specificity; Vancomycin - analogs & derivatives; Vancomycin - pharmacology
• ISSN: 1439-4227; 1439-7633
• DOI: 10.1002/cbic.200300557

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.