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 MM13902) were studied. Interestingly, the interaction between the Streptomyces cacaoi beta-lactamase and clavulanate indicated little irreversible inactivation. With sulbactam, irreversible inactivation was found to occur with the three studied enzymes, but no evidence for transiently 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, but with the S. cacaoi enzyme, no hydrolysis could be detected. A tentative 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.
Matagne
A
A
Laboratorie d'Enzymologie, Université de Liège, Sart Tilman, Belgium.
Ghuysen
M F
MF
Frère
J M
JM
D000192:Actinomycetales / Q000201:enzymology; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001665:Binding Sites; D019818:Clavulanic Acid; D002969:Clavulanic Acids / Q000494:pharmacology; D006868:Hydrolysis; D007700:Kinetics; D007769:Lactams; D012694:Serine; D013302:Streptomyces / Q000201:enzymology; D013407:Sulbactam / Q000494:pharmacology; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000378:metabolism; D047090:beta-Lactams
D000900:Anti-Bacterial Agents; D002969:Clavulanic Acids; D007769:Lactams; D065093:beta-Lactamase Inhibitors; D047090:beta-Lactams; D019818:Clavulanic Acid; D012694:Serine; C020786:olivanic acid; D001618:beta-Lactamases; D013407:Sulbactam