The Three-Dimensional Structure of VIM-2, a Zn-β-Lactamase from Pseudomonas aeruginosa in Its Reduced and Oxidised Form

I. Garcia-Saez, J. D. Docquier, G. M. Rossolini, O. Dideberg

Research output: Contribution to journalArticle


The crystal structures of the universally widespread metallo-β-lactamase (MBL) Verona integron-encoded MBL (VIM)-2 from Pseudomonas aeruginosa have been solved in their native form as well as in an unexpected oxidised form. This carbapenem-hydrolysing enzyme belongs to the so-called B1 subfamily of MBLs and shares the folding of αβ/βα sandwich, consisting of a core of β-sheet surrounded by α-helices. Surprisingly, it showed a high tendency to be strongly oxidised at the catalytic cysteine located in the Cys site, Cys221, which, in the oxidised structure, becomes a cysteinesulfonic residue. Its native structure was obtained only in the presence of Tris(2-carboxyethyl)phosphine. This oxidation might be a consequence of a lower affinity for the second Zn located in the Cys site that would also explain the observed susceptibility of VIM-2 to chelating agents. This modification, if present in nature, might play a role in catalytic down-regulation. Comparison between native and oxidised VIM-2 and a predicted model of VIM-1 (which shows one residue different in the Cys site compared with VIM-2) is performed to explain the different activities and antibiotic specificities.

Original languageEnglish
Pages (from-to)604-611
Number of pages8
JournalJournal of Molecular Biology
Issue number3
Publication statusPublished - Jan 18 2008



  • antibiotic resistance
  • crystal structure
  • cysteine oxidation
  • metallo-β-lactamase
  • metallo-β-lactamase inhibition

ASJC Scopus subject areas

  • Virology

Cite this