title: A kinetic study of NMC-A beta-lactamase, an Ambler class A carbapenemase also hydrolyzing cephamycins.
abstract: In order to analyze its kinetic parameters, an Ambler class A carbapenemase NMC-A was purified. NMC-A demonstrated unusually strong hydrolytic activity towards imipenem and meropenem. Moreover, it hydrolyzed cephamycins with kcat values uncommonly high for this class of beta-lactamases. Clavulanic acid and tazobactam had comparable inhibitory activity against NMC-A, whereas sulbactam was the least active inhibitor. Noticeably, NMC-A was more readily inhibited by brobactam. All these catalytic properties suggest that NMC-A possesses an original structure of its active site allowing hydrolysis of beta-lactams usually stable to the hydrolytic activity of class A beta-lactamases.
authors.affiliation: Service de Bactériologie-Virologie, Hôpital Lariboisière, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Mariotte-Boyer
authors.forename: M H
authors.initials: MH
authors.lastname: Nicolas-Chanoine
authors.forename: R
authors.initials: R
authors.lastname: Labia
mesh_terms: D001426:Bacterial Proteins; D001665:Binding Sites; D002513:Cephamycins; D019818:Clavulanic Acid; D002969:Clavulanic Acids / Q000494:pharmacology; D016972:Enterobacter cloacae / Q000201:enzymology / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004926:Escherichia coli / Q000235:genetics; D006868:Hydrolysis; D007700:Kinetics; D015394:Molecular Structure; D010397:Penicillanic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity; D013407:Sulbactam / Q000494:pharmacology; D000078142:Tazobactam; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D002513:Cephamycins; D002969:Clavulanic Acids; D004791:Enzyme Inhibitors; D011994:Recombinant Proteins; D065093:beta-Lactamase Inhibitors; D019818:Clavulanic Acid; C018008:brobactam; D010397:Penicillanic Acid; D001618:beta-Lactamases; C063912:carbapenemase; D013407:Sulbactam; D000078142:Tazobactam