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3znb

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==Overview==
==Overview==
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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.
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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==
==About this Structure==
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[[Category: Beta-lactamase]]
[[Category: Beta-lactamase]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: Concha, N.O.]]
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[[Category: Concha, N O.]]
[[Category: Herzberg, O.]]
[[Category: Herzberg, O.]]
[[Category: HG]]
[[Category: HG]]
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[[Category: zinc]]
[[Category: zinc]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb 3 10:52:41 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 19:11:53 2008''

Revision as of 17:11, 21 February 2008

Image:3znb.jpg

3znb, resolution 2.7Å

Drag the structure with the mouse to rotate

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 with , and as ligands. Active as Beta-lactamase, with EC number 3.5.2.6 Known structural/functional Sites: , and . 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

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