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| - | [[Image:1i2w.jpg|left|200px]] | + | {{Seed}} |
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| | {{STRUCTURE_1i2w| PDB=1i2w | SCENE= }} | | {{STRUCTURE_1i2w| PDB=1i2w | SCENE= }} |
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| - | '''BETA-LACTAMASE FROM BACILLUS LICHENIFORMIS BS3 COMPLEXED WITH CEFOXITIN'''
| + | ===BETA-LACTAMASE FROM BACILLUS LICHENIFORMIS BS3 COMPLEXED WITH CEFOXITIN=== |
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| - | ==Overview==
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| - | The Bacillus licheniformis BS3 beta-lactamase catalyzes the hydrolysis of the beta-lactam ring of penicillins, cephalosporins, and related compounds. The production of beta-lactamases is the most common and thoroughly studied cause of antibiotic resistance. Although they escape the hydrolytic activity of the prototypical Staphylococcus aureus beta-lactamase, many cephems are good substrates for a large number of beta-lactamases. However, the introduction of a 7alpha-methoxy substituent, as in cefoxitin, extends their antibacterial spectrum to many cephalosporin-resistant Gram-negative bacteria. The 7alpha-methoxy group selectively reduces the hydrolytic action of many beta-lactamases without having a significant effect on the affinity for the target enzymes, the membrane penicillin-binding proteins. We report here the crystallographic structures of the BS3 enzyme and its acyl-enzyme adduct with cefoxitin at 1.7 A resolution. The comparison of the two structures reveals a covalent acyl-enzyme adduct with perturbed active site geometry, involving a different conformation of the omega-loop that bears the essential catalytic Glu166 residue. This deformation is induced by the cefoxitin side chain whose position is constrained by the presence of the alpha-methoxy group. The hydrolytic water molecule is also removed from the active site by the 7beta-carbonyl of the acyl intermediate. In light of the interactions and steric hindrances in the active site of the structure of the BS3-cefoxitin acyl-enzyme adduct, the crucial role of the conserved Asn132 residue is confirmed and a better understanding of the kinetic results emerges.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_11827533}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 11827533 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_11827533}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Hydrolase]] | | [[Category: Hydrolase]] |
| | [[Category: Serine beta-lactamase]] | | [[Category: Serine beta-lactamase]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 19:30:23 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 10:19:45 2008'' |
Revision as of 07:19, 1 July 2008
Template:STRUCTURE 1i2w
BETA-LACTAMASE FROM BACILLUS LICHENIFORMIS BS3 COMPLEXED WITH CEFOXITIN
Template:ABSTRACT PUBMED 11827533
About this Structure
1I2W is a Single protein structure of sequence from Bacillus licheniformis. Full crystallographic information is available from OCA.
Reference
Crystal structures of the Bacillus licheniformis BS3 class A beta-lactamase and of the acyl-enzyme adduct formed with cefoxitin., Fonze E, Vanhove M, Dive G, Sauvage E, Frere JM, Charlier P, Biochemistry. 2002 Feb 12;41(6):1877-85. PMID:11827533
Page seeded by OCA on Tue Jul 1 10:19:45 2008
