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| - | [[Image:1znb.gif|left|200px]] | + | {{Seed}} |
| | + | [[Image:1znb.png|left|200px]] |
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| | {{STRUCTURE_1znb| PDB=1znb | SCENE= }} | | {{STRUCTURE_1znb| PDB=1znb | SCENE= }} |
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| - | '''METALLO-BETA-LACTAMASE'''
| + | ===METALLO-BETA-LACTAMASE=== |
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| - | ==Overview==
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| - | BACKGROUND: The metallo-beta-lactamase from Bacteroides fragilis hydrolyzes a wide range of beta-lactam antibiotics, and is not clinically susceptible to any known beta-lactamase inhibitors. B. fragilis is associated with post-surgery hospital infections, and there has been a recent report of plasmid-mediated dissemination of the enzyme. Effective inhibitors are therefore urgently needed. Knowledge of the three-dimensional structure will aid in the drug design effort. RESULTS: The crystal structure of the enzyme has been determined by using multiwavelength anomalous diffraction at the zinc absorption edge and refined to 1.85 A resolution. The structure is a four-layer alpha/beta/beta/alpha molecule. The active site, found at the edge of the beta sandwich contains a binuclear zinc center with several novel features. One zinc is tetrahedrally coordinated, the other has a trigonal bipyramidal coordination; a water/hydroxide molecule serves as a ligand for both metals. The residues that coordinate the two zincs are invariant in all metallo-beta-lactamases that have been sequenced, except for two conservative replacements. Despite the existence of the pattern for binuclear zinc binding, the reported structure of the Bacillus cereus enzyme contains only a single zinc. CONCLUSIONS: Structural analysis indicates that affinity for the penta-coordinated zinc can be modulated by neighboring residues, perhaps explaining the absence of the second zinc in the B. cereus structure. Models of bound substrates suggest that the active-site channel can accommodate a wide variety of beta-lactams. We propose that the zinc cluster prepares an hydroxide, probably the hydroxide that ligates both zincs, for nucleophilic attack on the carbonyl carbon atom of the beta-lactam. The resulting negatively charged tetrahedral intermediate implicated in catalysis is stabilized by an oxyanion hole formed by the side chain of the invariant Asn 193 and the tetrahedral zinc.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_8805566}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 8805566 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_8805566}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Herzberg, O.]] | | [[Category: Herzberg, O.]] |
| | [[Category: Metallo beta-lactamase zinc]] | | [[Category: Metallo beta-lactamase zinc]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 17:50:18 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 12:11:10 2008'' |
Revision as of 09:11, 29 July 2008
Template:STRUCTURE 1znb
METALLO-BETA-LACTAMASE
Template:ABSTRACT PUBMED 8805566
About this Structure
1ZNB is a Single protein structure of sequence from Bacteroides fragilis. Full crystallographic information is available from OCA.
Reference
Crystal structure of the wide-spectrum binuclear zinc beta-lactamase from Bacteroides fragilis., Concha NO, Rasmussen BA, Bush K, Herzberg O, Structure. 1996 Jul 15;4(7):823-36. PMID:8805566
Page seeded by OCA on Tue Jul 29 12:11:10 2008
