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

A classification scheme for beta -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 broad-spectrum beta -lactamases that are generally inhibited by active site-directed beta -lactamase inhibitors; and the group 3 metallo- beta -lactamases that hydrolyze penicillins, cephalosporins, and carbapenems and that are poorly inhibited by almost all beta -lactam-containing molecules. Functional characteristics have been correlated with molecular structure in a dendrogram for those enzymes with known amino acid sequences. beta -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 C-N bonds ... separated on the basis of the substrate:... cyclic amides". These enzymes are the major cause of bacterial resistance to beta -lactam antibiotics and have been the subject of extensive microbiological, biochemical, and genetic investigations. Investigators have described more than 190 unique bacterial proteins.