3znb
From Proteopedia
| |||||||
| , resolution 2.7Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | , and | ||||||
| Ligands: | , , | ||||||
| Gene: | CCRA3 (WITHOUT SIGNAL SEQUENCE) (Bacteroides fragilis) | ||||||
| Activity: | Beta-lactamase, with EC number 3.5.2.6 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
METALLO-BETA-LACTAMASE (ZN, HG-BOUND FORM)
Overview
The metallo-beta-lactamases require zinc or cadmium for hydrolyzing beta-lactam antibiotics and are inhibited by mercurial compounds. To data, there are no clinically useful inhibitors of this class of enzymes. The crystal structure of the Zn(2+)-bound enzyme from Bacteroides fragilis contains a binuclear zinc center in the active site. A hydroxide, coordinated to both zinc atoms, is proposed as the moiety that mounts the nucleophilic attack on the carbonyl carbon atom of the beta-lactam ring. To study the metal coordination further, the crystal structures of a Cd(2+)-bound enzyme and of an Hg(2+)-soaked zinc-containing enzyme have been determined at 2.1 A and 2.7 A, respectively. Given the diffraction resolution, the Cd(2+)-bound enzyme exhibits the same active-site architecture as that of the Zn(2+)-bound enzyme, consistent with the fact that both forms are enzymatically active. The 10-fold reduction in activity of the Cd(2+)-bound molecule compared with the Zn(2+)-bound enzyme is attributed to fine differences in the charge distribution due to the difference in the ionic radii of the two metals. In contrast, in the Hg(2+)-bound structure, one of the zinc ions, Zn2, was ejected, and the other zinc ion, Zn1, remained in the same site as in the 2-Zn(2+)-bound structure. Instead of the ejected zinc, a mercury ion binds between Cys 104 and Cys 181, 4.8 A away from Zn1 and 3.9 A away from the site where Zn2 is located in the 2-Zn(2+)-bound molecule. The perturbed binuclear metal cluster explains the inactivation of the enzyme by mercury compounds.
About this Structure
3ZNB is a Single protein structure of sequence from Bacteroides fragilis. Full crystallographic information is available from OCA.
Reference
Crystal structures of the cadmium- and mercury-substituted metallo-beta-lactamase from Bacteroides fragilis., Concha NO, Rasmussen BA, Bush K, Herzberg O, Protein Sci. 1997 Dec;6(12):2671-6. PMID:9416622
Page seeded by OCA on Mon Mar 31 05:36:41 2008
