4NQ2

Structure of Zn(II)-bound metallo-beta-lactamse VIM-2 from Pseudomonas aeruginosa

Summary for 4NQ2

• Entry DOI: 10.2210/pdb4nq2/pdb
• Related: 1ko2 1ko3 2yz3
• Descriptor: Beta-lactamase class B VIM-2, ZINC ION, ACETATE ION, ... (4 entities in total)
• Functional Keywords: metallo-beta-lactamase, hydrolase, zinc binding
• Biological source: Pseudomonas aeruginosa
• Total number of polymer chains: 1
• Total formula weight: 28095.50

Authors

Aitha, M.,Nix, J.C.,Crowder, M.W.,Page, R.C. (deposition date: 2013-11-23, release date: 2014-11-12, Last modification date: 2023-09-20)

Primary citation

Aitha, M.,Marts, A.R.,Bergstrom, A.,Moller, A.J.,Moritz, L.,Turner, L.,Nix, J.C.,Bonomo, R.A.,Page, R.C.,Tierney, D.L.,Crowder, M.W.
Biochemical, Mechanistic, and Spectroscopic Characterization of Metallo-beta-lactamase VIM-2.
Biochemistry, 53:7321-7331, 2014

PubMed Abstract: This study examines metal binding to metallo-β-lactamase VIM-2, demonstrating the first successful preparation of a Co(II)-substituted VIM-2 analogue. Spectroscopic studies of the half- and fully metal loaded enzymes show that both Zn(II) and Co(II) bind cooperatively, where the major species present, regardless of stoichiometry, are apo- and di-Zn (or di-Co) enzymes. We determined the di-Zn VIM-2 structure to a resolution of 1.55 Å, and this structure supports results from spectroscopic studies. Kinetics, both steady-state and pre-steady-state, show that VIM-2 utilizes a mechanism that proceeds through a very short-lived anionic intermediate when chromacef is used as the substrate. Comparison with other B1 enzymes shows that those that bind Zn(II) cooperatively are better poised to protonate the intermediate on its formation, compared to those that bind Zn(II) non-cooperatively, which uniformly build up substantial amounts of the intermediate.

PubMed: 25356958
DOI: 10.1021/bi500916y

Experimental method

X-RAY DIFFRACTION (1.55 Å)