title: Biochemical characterization of IMP-30, a metallo-β-lactamase with enhanced activity toward ceftazidime.
abstract: IMP-type enzymes constitute a clinically important family of metallo-β-lactamases that has grown dramatically in the past decade to its current 45 known members. Here, we report the biochemical characterization of IMP-30 in comparison to IMP-1, from which it deviates by a single E59K mutation. Kinetics, MIC assays, docking, and molecular dynamics simulations support a scenario in which Lys59 interacts with the ceftazidime R1 group, resulting in increased water access and enhanced turnover and MIC of ceftazidime.
authors.affiliation: Department of Biological Sciences, College of Science, California State Polytechnic University, Pomona, California, USA.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Pegg
authors.forename: Eleanor M
authors.initials: EM
authors.lastname: Liu
authors.forename: Alecander E
authors.initials: AE
authors.lastname: Lacuran
authors.forename: Peter
authors.initials: P
authors.lastname: Oelschlaeger
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D002442:Ceftazidime / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D056004:Molecular Dynamics Simulation; D009154:Mutation; D001618:beta-Lactamases / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D002442:Ceftazidime; D001618:beta-Lactamases