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Publication Abstract from PubMed

Dissemination of Acinetobacter baumannii strains harboring class D beta-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 beta-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.

Structural Basis for Carbapenemase Activity of the OXA-23 beta-Lactamase from Acinetobacter baumannii.,Smith CA, Antunes NT, Stewart NK, Toth M, Kumarasiri M, Chang M, Mobashery S, Vakulenko SB Chem Biol. 2013 Sep 19;20(9):1107-15. doi: 10.1016/j.chembiol.2013.07.015. Epub, 2013 Sep 5. PMID:24012371^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.