Vol.61 No.3 May 2013
Extended-Spectrum β-Lactamase: a strategy to expand substrate specificity from the viewpoint of structural biology
Department of Science, Yamagata University, 1-4-12 Kojirakawa, Yamagata, Japan
Abstract
β-Lactamases are bacterial hydrolytic enzymes that inactivate β-lactams. They are classified into four classes from A to D, based on the amino acid sequence. With the clinical use of many different β-lactams, β-lactamases that can hydrolyze a broad range of β-lactams have emerged. These enzymes with broad substrate specificity are called "Extended-spectrum β-lactamases (ESBL)". In class A, many ESBLs that can hydrolyze third-generation cephalosporins have been reported. Moreover, several enzymes with hydrolyzing activity toward carbapenems, the β-lactam antibiotics that are stable to most of the β-lactamases and are therefore known as the "last resort", have also emerged. Thus, the molecular evolution against new antibiotics seems to be ongoing. In this review, I focus on the structural features of class A enzymes, and introduce how these protein molecules acquire hydrolytic activity toward a broader range of β-lactams.
Key word
extended-spectrum β-lactamases, carbapenemases, structure
Received
April 1, 2013
Accepted
April 5, 2013
Jpn. J. Chemother. 61 (3): 287-291, 2013
