Resistance mechanism to an uncompetitive inhibitor of a single-substrate, single-product enzyme: a study of Helicobacter pylori glutamate racemase

摘要: Two independent series of inhibitors Helicobacter pylori glutamate racemase (MurI) were characterized for their kinetic mechanism, and one was used to generate resistant mutants in vitro. Mutant MurI enzymes from these strains by structural, genetic, biophysical methods. Both inhibitor series, pyrazolopyrimidinediones benzodiazepines, are uncompetitive with respect the substrate, resistance mutations found act reducing affinity thereby pool enzyme–substrate complex available binding inhibitor, while still allowing sufficient activity peptidoglycan construction. Uncompetitive a single-substrate, single-product enzyme rare, this work gives insight into an remarkable mechanism. This article will discuss projected clinical impact H. on types inhibitors.