INTERACTIONS BETWEEN ACTIVE-SITE-SERINE BETA-LACTAMASES AND MECHANISM-BASED INACTIVATORS - A KINETIC-STUDY AND AN OVERVIEW

The interactions between three class A beta-lactamases and three beta- lactamase inactivators (clavulanic acid, sulbactam and olivanic acid M M13902) were studied. Interestingly, the interaction between the Strep tomyces cacaoi beta-lactamase and clavulanate indicated little irrever sible inactivation. With sulbactam, irreversible inactivation was foun d to occur with the three studied enzymes, but no evidence for transie ntly inactivated adducts was found. Irreversible inactivation of the S . albus G and S. cacaoi enzymes was particularly slow. With olivanate, irreversible inactivation was also observed with the three enzymes, b ut with the S. cacaoi enzyme, no hydrolysis could be detected. A tenta tive summary of the results found in the literature is also presented (including 6 beta-halogenopenicillanates), and the general conclusions underline the diversity of the mechanisms and the wide variations of the rate constants observed when class A beta-lactamases interact with beta-lactamase inactivators, in agreement with the behaviours of the same enzymes towards their good and poor substrates.