1ko2 | pdb_00001ko2
VIM-2, a Zn-beta-lactamase from Pseudomonas aeruginosa with an oxidized Cys (cysteinesulfonic)
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Overview
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.
About this Structure
1KO2 is a Single protein structure of sequence from Pseudomonas aeruginosa with ZN and ACT as ligands. Active as Hydrolase, with EC number 3.5.2.6 Full crystallographic information is available from OCA.
Reference
The three-dimensional structure of VIM-2, a Zn-beta-lactamase from Pseudomonas aeruginosa in its reduced and oxidised form., Garcia-Saez I, Docquier JD, Rossolini GM, Dideberg O, J Mol Biol. 2008 Jan 18;375(3):604-11. Epub 2007 Nov 13. PMID:18061205
Page seeded by OCA on Wed Jan 23 11:01:16 2008
