The three-dimensional structure of VIM-2, a Zn-beta-lactamase from Pseudomonas aeruginosa in its reduced and oxidised form.
J Mol Biol
; 375(3): 604-11, 2008 Jan 18.
Article
en En
| MEDLINE
| ID: mdl-18061205
The crystal structures of the universally widespread metallo-beta-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 alpha beta/beta alpha sandwich, consisting of a core of beta-sheet surrounded by alpha-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.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Conformación Proteica
/
Pseudomonas aeruginosa
/
Proteínas Bacterianas
/
Zinc
/
Beta-Lactamasas
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
J Mol Biol
Año:
2008
Tipo del documento:
Article
País de afiliación:
Francia
Pais de publicación:
Países Bajos