title: Kinetics of the Interaction between BAL29880 and LK157 and the Class C β-Lactamase CHE-1.
abstract: The chromosome-encoded class C β-lactamase CHE-1 produced by Enterobacter cloacae exhibits a lower sensitivity to avibactam than the P99 enzyme from which it is derived by a 6-residue deletion in the H-10 helix. In the present study, we investigated the sensitivity of CHE-1 to two other β-lactamase inhibitors: LK-157 (or Lek 157), a tricyclic β-lactam, and BAL29880, a bridged monobactam. With both compounds, the second-order rate constants for inactivation were significantly lower for CHE-1, which can thus be considered an inactivator-resistant mutant of P99. However, the second-order rate constant for the inactivation by BAL29880 probably remains adequate for a rather rapid reaction with CHE-1 in the absence of protection by the substrate.
authors.affiliation: Centre for Protein Engineering, Université de Liège, Liège, Belgium.
authors.forename: Adriana
authors.initials: A
authors.lastname: Fernea
authors.affiliation: Centre for Protein Engineering, Université de Liège, Liège, Belgium.
authors.forename: Moreno
authors.initials: M
authors.lastname: Galleni
authors.affiliation: Centre for Protein Engineering, Université de Liège, Liège, Belgium jmfrere@ulg.ac.be.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Frère
mesh_terms: D053961:Azabicyclo Compounds / Q000494:pharmacology*; D015780:Carbapenems / Q000494:pharmacology*; D016972:Enterobacter cloacae / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D008997:Monobactams / Q000494:pharmacology*; D010671:Phenylurea Compounds / Q000494:pharmacology*; D065093:beta-Lactamase Inhibitors / Q000494:pharmacology*; D001618:beta-Lactamases / Q000235:genetics* / Q000378:metabolism
chemical_list: D053961:Azabicyclo Compounds; C000612851:BAL29880; D015780:Carbapenems; C539935:LK-157; D008997:Monobactams; D010671:Phenylurea Compounds; D065093:beta-Lactamase Inhibitors; C543519:avibactam; D001618:beta-Lactamases