4JF6

Structure of OXA-23 at pH 7.0

Summary for 4JF6

• Entry DOI: 10.2210/pdb4jf6/pdb
• Related: 4JF4 4JF5
• Descriptor: Beta-lactamase, POTASSIUM ION, CHLORIDE ION, ... (5 entities in total)
• Functional Keywords: beta-lactamase, hydrolase
• Biological source: Acinetobacter baumannii
• Total number of polymer chains: 1
• Total formula weight: 27976.97

Authors

Smith, C.A.,Vakulenko, S.B. (deposition date: 2013-02-27, release date: 2013-09-25, Last modification date: 2013-10-09)

Primary citation

Smith, C.A.,Antunes, N.T.,Stewart, N.K.,Toth, M.,Kumarasiri, M.,Chang, M.,Mobashery, S.,Vakulenko, S.B.
Structural Basis for Carbapenemase Activity of the OXA-23 beta-Lactamase from Acinetobacter baumannii.
Chem.Biol., 20:1107-1115, 2013

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.

PubMed: 24012371
DOI: 10.1016/j.chembiol.2013.07.015

Experimental method

X-RAY DIFFRACTION (2.5 Å)