CATALYTIC PROPERTIES OF CLASS-A BETA-LACTAMASES - EFFICIENCY AND DIVERSITY

beta-Lactamases are the main cause of bacterial resistance to penicill ins, cephalosporins and related beta-lactam compounds. These enzymes i nactivate the antibiotics by hydrolysing the amide bond of the beta-la ctam ring. Class A beta-lactamases are the most widespread enzymes and are responsible for numerous failures in the treatment of infectious diseases. The introduction of new beta-lactam compounds, which are mea nt to be 'beta-lactamase-stable' or beta-lactamase inhibitors, is thus continuously challenged either by point mutations in the ubiquitous T EM and SHV plasmid-borne beta-lactamase genes or by the acquisition of new genes coding for beta-lactamases with different catalytic propert ies. On the basis of the X-ray crystallography structures of several c lass A beta-lactamases, including that of the clinically relevant TEM- 1 enzyme, it has become possible to analyse how particular structural changes in the enzyme structures might modify their catalytic properti es. However, despite the many available kinetic, structural and mutage nesis data, the factors explaining the diversity of the specificity pr ofiles of class A beta-lactamases and their amazing catalytic efficien cy have not been thoroughly elucidated. The detailed understanding of these phenomena constitutes the cornerstone for the design of future g enerations of antibiotics.