2WHG

Crystal Structure of the Di-Zinc Metallo-beta-lactamase VIM-4 from Pseudomonas aeruginosa

Summary for 2WHG

• Entry DOI: 10.2210/pdb2whg/pdb
• Descriptor: VIM-4 METALLO-BETA-LACTAMASE, ZINC ION, CITRATE ANION, ... (4 entities in total)
• Functional Keywords: hydrolase, alpha-beta/beta-alpha fold
• Biological source: PSEUDOMONAS AERUGINOSA
• Total number of polymer chains: 2
• Total formula weight: 49532.14

Authors

Lassaux, P.,Traore, D.A.K.,Galleni, M.,Ferrer, J.L. (deposition date: 2009-05-05, release date: 2010-05-19, Last modification date: 2023-12-13)

Primary citation

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.
Biochemical and Structural Characterization of the Subclass B1 Metallo-{Beta}-Lactamase Vim-4.
Antimicrob.Agents Chemother., 55:1248-, 2011

PubMed Abstract: The metallo-β-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 Zn²+ at concentrations ranging from 0.4 to 100 μM 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 Å. 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 Zn²+ ions have a pronounced stabilizing effect on the enzyme and are necessary for preserving the structure.

PubMed: 21149620
DOI: 10.1128/AAC.01486-09

Experimental method

X-RAY DIFFRACTION (1.9 Å)