Download MendeleyBiochemical and Structural Characterization of the Subclass B1 Metallo-{Beta}-Lactamase Vim-4.
Lassaux, P., Traore, D.A.K., Loisel, E., Favier, A., Docquier, J.D., Sohier, J.S., Laurent, C., Bebrone, C., Frere, J.M., Ferrer, J.L., Galleni, M.(2011) Antimicrob Agents Chemother 55: 1248
- PubMed: 21149620
- DOI: https://doi.org/10.1128/AAC.01486-09
- Primary Citation of Related Structures:
2WHG - PubMed Abstract:
The metallo-¦Â-lactamase VIM-4, mainly found in Pseudomonas aeruginosa or Acinetobacter baumannii, was produced in Escherichia coli and characterized by biochemical and X-ray techniques. A detailed kinetic study performed in the presence of Zn?+ at concentrations ranging from 0.4 to 100 ¦̀M showed that VIM-4 exhibits a kinetic profile similar to the profiles of VIM-2 and VIM-1. However, VIM-4 is more active than VIM-1 against benzylpenicillin, cephalothin, nitrocefin, and imipenem and is less active than VIM-2 against ampicillin and meropenem. The crystal structure of the dizinc form of VIM-4 was solved at 1.9 ?. The sole difference between VIM-4 and VIM-1 is found at residue 228, which is Ser in VIM-1 and Arg in VIM-4. This substitution has a major impact on the VIM-4 catalytic efficiency compared to that of VIM-1. In contrast, the differences between VIM-2 and VIM-4 seem to be due to a different position of the flapping loop and two substitutions in loop 2. Study of the thermal stability and the activity of the holo- and apo-VIM-4 enzymes revealed that Zn?+ ions have a pronounced stabilizing effect on the enzyme and are necessary for preserving the structure.
Organizational Affiliation:
Laboratoire de Macromolecules Biologiques, Centre d'Ing¨¦nierie des Prot¨¦ines, Universit¨¦ de Li¨¨ge, All¨¦e du 6 Ao?t B6, Sart-Tilman, 4000 Li¨¨ge, Belgium.
