The structure of β-lactamases

TLDR

Beta‑lactamases, widespread in Gram‑positive and Gram‑negative bacteria, inactivate penicillins and cephalosporins by opening the beta‑lactam ring; many variants are distinguished by catalytic and molecular properties, but only amino‑acid sequence analysis enables phylogenetic classification, revealing that known enzymes fall into a class A homology group and a distinct class B (Bacillus cereus β‑lactamase II) that appears structurally unrelated. The authors predict that further sequence analysis will uncover additional classes needed to account for beta‑lactamases with distinctive molecular and mechanistic properties. Evidence indicates that beta‑lactamases have a polyphyletic origin.

Abstract

The beta-lactamases are widely distributed in both Gram-positive and Gram-negative bacteria. They all inactivate penicillins and cephalosporins by opening the beta-lactam ring. Many varieties of the enzyme can be distinguished on the basis of their catalytic and molecular properties, but only amino acid sequence determination gives information upon which a molecular phylogeny can be based. The present evidence suggests that the beta-lactamases have a polyphyletic origin. All the beta-lactamases of currently known amino acid sequence belong to one homology group, here called class A enzymes. Class B consists of the mechanistically distinct Bacillus cereus beta-lactamase II, which preliminary partial sequence analysis suggests to be structurally unrelated to the class A enzymes. It is predicted that sequence analysis will show that further classes will need to be created to account for particular beta-lactamases of distinctive molecular and mechanistic properties.