Crystal structure of the OXA-48 beta-lactamase reveals mechanistic diversity among class D carbapenemases

Chem Biol. 2009 May 29;16(5):540-7. doi: 10.1016/j.chembiol.2009.04.010.


Carbapenem-hydrolyzing class D beta-lactamases (CHDLs) are enzymes found in important Gram-negative pathogens (mainly Acinetobacter baumannii and Enterobacteriaceae) that confer resistance to beta-lactam antibiotics, and notably carbapenems. The crystal structure of the OXA-48 carbapenemase was determined at pH 7.5 and at a resolution of 1.9 A. Surprisingly, and by contrast with OXA-24, the only other CHDL of known crystal structure, the structure of OXA-48 was similar to OXA-10, an enzyme devoid of carbapenemase activity, indicating that the hydrolysis of these compounds could depend on subtle changes in the active site region. Moreover, the active site groove of OXA-48 was different from that of OXA-24 in shape, dimensions, and charge distribution. Molecular dynamics pointed to the functional relevance of residues located in or close to the beta5-beta6 loop and allowed us to propose a mechanism for carbapenem hydrolysis by OXA-48.

MeSH terms

  • Bacterial Proteins / chemistry
  • Bacterial Proteins / classification
  • Catalytic Domain
  • Computer Simulation
  • Crystallography, X-Ray
  • Kinetics
  • Protein Structure, Quaternary
  • beta-Lactamases / chemistry*
  • beta-Lactamases / classification


  • Bacterial Proteins
  • beta-Lactamases
  • carbapenemase

Associated data

  • PDB/3HBR