Structural basis for carbapenemase activity of the OXA-23 ?-lactamase from Acinetobacter baumannii.

ABSTRACT: Dissemination of Acinetobacter baumannii strains harboring class D ?-lactamases producing resistance to carbapenem antibiotics severely limits our ability to treat deadly Acinetobacter infections. Susceptibility determination in the A. baumannii background and kinetic studies with a homogeneous preparation of OXA-23 ?-lactamase, the major carbapenemase present in A. baumannii, document the ability of this enzyme to manifest resistance to last-resort carbapenem antibiotics. We also report three X-ray structures of OXA-23: apo OXA-23 at two different pH values, and wild-type OXA-23 in complex with meropenem, a carbapenem substrate. The structures and dynamics simulations reveal an important role for Leu166, whose motion regulates the access of a hydrolytic water molecule to the acyl-enzyme species in imparting carbapenemase activity.

SUBMITTER: Smith CA 

PROVIDER: S-EPMC3888872 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature