4JF4

OXA-23 meropenem complex

Summary for 4JF4

• Entry DOI: 10.2210/pdb4jf4/pdb
• Related: 4JF5 4JF6
• Descriptor: Beta-lactamase, 1,2-ETHANEDIOL, (4R,5S)-3-{[(3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-yl]sulfanyl}-5-[(2S,3R)-3-hydroxy-1-oxobutan-2-yl]-4-methyl-4,5-d ihydro-1H-pyrrole-2-carboxylic acid, ... (4 entities in total)
• Functional Keywords: beta-lactamase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Acinetobacter baumannii
• Total number of polymer chains: 2
• Total formula weight: 56126.89

Authors

Smith, C.A.,Vakulenko, S.B.,Toth, M. (deposition date: 2013-02-27, release date: 2013-09-25, Last modification date: 2024-10-09)

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 (2.14 Å)