Functional and structural analyses of IMP-27 metallo-β-lactamase: evolution of IMP-type enzymes to overcome Zn(II) deprivation.

ABSTRACT: IMP-type metallo-β-lactamases are di-Zn(II) enzymes that can inactivate a wide range of bicyclic β-lactam agents used in clinical practice. IMP-27 shares 82% amino acid sequence identity with IMP-1, the first IMP-type enzyme identified. Herein, we conducted structural determination, kinetic, and chelating agent resistance analyses of IMP-27. Once determined, IMP-27 was then compared to its mutant, namely, G262S, and IMP-1. Crystallographic structural analysis of IMP-27 showed an overall structure comparable to that of IMP-1 and other IMP-type enzymes; the positions of the zinc (Zn) ions varied across enzymes. Kinetic analysis showed that IMP-27 had lower catalytic efficiency against penicillins, ceftazidime, cephalexin, and imipenem than IMP-1; however, it had higher affinity and catalytic

SUBMITTER: Kato Y 

PROVIDER: S-EPMC11619291 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature