Download MendeleyStructural Basis for Carbapenemase Activity of the OXA-23 beta-Lactamase from Acinetobacter baumannii.
Smith, C.A., Antunes, N.T., Stewart, N.K., Toth, M., Kumarasiri, M., Chang, M., Mobashery, S., Vakulenko, S.B.(2013) Chem Biol 20: 1107-1115
- PubMed: 24012371
- DOI: https://doi.org/10.1016/j.chembiol.2013.07.015
- Primary Citation of Related Structures:
4JF4, 4JF5, 4JF6 - PubMed Abstract:
Dissemination of Acinetobacter baumannii strains harboring class D β-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 β-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.
Organizational Affiliation:
Stanford Synchrotron Radiation Lightsource, Stanford University, Menlo Park, CA 94025, USA. Electronic address: [email protected].
