3ZNB

METALLO-BETA-LACTAMASE (ZN, HG-BOUND FORM)

Summary for 3ZNB

• Entry DOI: 10.2210/pdb3znb/pdb
• Descriptor: METALLO-BETA-LACTAMASE, ZINC ION, MERCURY (II) ION, ... (5 entities in total)
• Functional Keywords: hydrolase, beta-lactamase, metallo beta-lactamase, mercury, zinc
• Biological source: Bacteroides fragilis
• Total number of polymer chains: 2
• Total formula weight: 51118.97

Authors

Concha, N.O.,Herzberg, O. (deposition date: 1997-10-15, release date: 1998-01-28, Last modification date: 2024-05-22)

Primary citation

Concha, N.O.,Rasmussen, B.A.,Bush, K.,Herzberg, O.
Crystal structures of the cadmium- and mercury-substituted metallo-beta-lactamase from Bacteroides fragilis.
Protein Sci., 6:2671-2676, 1997

PubMed Abstract: 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.

PubMed: 9416622

Experimental method

X-RAY DIFFRACTION (2.7 Å)