2znb
From Proteopedia
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==Overview== | ==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 ... | + | 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== | ||
| - | 2ZNB is a | + | 2ZNB is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bacteroides_fragilis Bacteroides fragilis] with CD and NA as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Beta-lactamase Beta-lactamase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.2.6 3.5.2.6] Structure known Active Sites: CD1, CD2 and NA. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2ZNB OCA]. |
==Reference== | ==Reference== | ||
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[[Category: metallo beta-lactamase]] | [[Category: metallo beta-lactamase]] | ||
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 14:40:12 2007'' |
Revision as of 12:34, 5 November 2007
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METALLO-BETA-LACTAMASE (CADMIUM-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
2ZNB is a Single protein structure of sequence from Bacteroides fragilis with CD and NA as ligands. Active as Beta-lactamase, with EC number 3.5.2.6 Structure known Active Sites: CD1, CD2 and NA. 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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