Jed F. Fisher and Shahriar Mobashery Pages 401 - 407 ( 7 )
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., Three, Decades, of, the, Class, A, β-Lactamase, Acyl-Enzyme
Department of Chemistry&Biochemistry, University of Notre Dame, Notre Dame IN 46556-5670, USA.