A functional classification scheme for beta-lactamases and its correlation with molecular structure

Abstract

A classification scheme for b-lactamases based on functional characteristics is presented. Three major groups of enzymes are defined by their substrate and inhibitor profiles: group 1 cephalosporinases that are not well inhibited by clavulanic acid; group 2 penicillinases, cephalosporinases, and broadspectrum b-lactamases that are generally inhibited by active site-directed b-lactamase inhibitors; and the group 3 metallob-lactamases that hydrolyze penicillins, cephalosporins, and carbapenems and that are poorly inhibited by almost all b-lactam-containing molecules. Functional characteristics have been correlated with molecular structure in a dendrogram for those enzymes with known amino acid sequences. b-Lactamases (EC 3.5.2.6) have been designated by the Nomenclature Committee of the International Union of Biochemistry as ‘‘enzymes hydrolysing amides, amidines and other CON bonds . . . separated on the basis of the substrate: . . . cyclic amides’’ (323). These enzymes are the major cause of bacterial resistance to b-lactam antibiotics and have been the subject of extensive microbiological, biochemical, and genetic investigations. Investigators have described more than 190 unique bacterial proteins with the ability to interact with the variety of b-lactam-containing molecules that can serve as sub-