Abstract
The discovery that the mechanism of β-lactam hydrolysis catalyzed by the class A (active site serinedependent) β-lactamases proceeds via an acyl-enzyme intermediate was made thirty years ago. Since this discovery, the active site circumstance that enables acylation of the active site serine and further enables hydrolytic deacylation of the acyl-serine intermediate, has received extraordinary scrutiny. The justification for this scrutiny is the direct relevance of the β-lactamases to the manifestation of bacterial resistance to the β-lactam antibiotics, and the subsequent (to the discovery of the β-lactamase acyl-enzyme) recognition of the direct evolutionary relationship between the serine β-lactamase acyl-enzyme, and the penicillin binding protein acyl-enzyme that is key to β-lactam antibiotic activity. This short review describes the early events leading to the recognition that serine β-lactamase catalysis proceeds via an acyl-enzyme intermediate, and summarizes several of the key mechanistic studies — including infrared spectroscopy, cryoenzymology, β- lactam design, and x-ray crystallography — that have been exploited to understand this pivotal catalytic intermediate.
Current Protein & Peptide Science
Title: Three Decades of the Class A β-Lactamase Acyl-Enzyme
Volume: 10 Issue: 5
Author(s): Jed F. Fisher and Shahriar Mobashery
Affiliation:
Abstract: The discovery that the mechanism of β-lactam hydrolysis catalyzed by the class A (active site serinedependent) β-lactamases proceeds via an acyl-enzyme intermediate was made thirty years ago. Since this discovery, the active site circumstance that enables acylation of the active site serine and further enables hydrolytic deacylation of the acyl-serine intermediate, has received extraordinary scrutiny. The justification for this scrutiny is the direct relevance of the β-lactamases to the manifestation of bacterial resistance to the β-lactam antibiotics, and the subsequent (to the discovery of the β-lactamase acyl-enzyme) recognition of the direct evolutionary relationship between the serine β-lactamase acyl-enzyme, and the penicillin binding protein acyl-enzyme that is key to β-lactam antibiotic activity. This short review describes the early events leading to the recognition that serine β-lactamase catalysis proceeds via an acyl-enzyme intermediate, and summarizes several of the key mechanistic studies — including infrared spectroscopy, cryoenzymology, β- lactam design, and x-ray crystallography — that have been exploited to understand this pivotal catalytic intermediate.
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Cite this article as:
Fisher F. Jed and Mobashery Shahriar, Three Decades of the Class A β-Lactamase Acyl-Enzyme, Current Protein & Peptide Science 2009; 10 (5) . https://dx.doi.org/10.2174/138920309789351967
DOI https://dx.doi.org/10.2174/138920309789351967 |
Print ISSN 1389-2037 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5550 |
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