Inactivation of Bacillus cereus 569/H beta-lactamase I by 6-beta-(trifluoromethane sulfonyl)amidopenicillanic acid sulfone and its N-methyl derivative.

6-beta-(Trifluoromethane sulfonyl)amidopenicillanic acid sulfone and its N-methyl derivative were found to be potent inhibitors of Bacillus cereus 569/H beta-lactamase I. The rate of the inactivation of the enzyme by both compounds was found to increase with the decreasing pH of the reaction medium. The reaction of the enzyme with 6-beta-(trifluoromethane sulfonyl)amidopenicillanic acid sulfone was found to be irreversible at the pH values investigated. In contrast, the reaction with the N-methyl derivative at neutral pH was consistent with the partitioning of the acyl enzyme intermediate in three pathways which included (a) deacylation to yield active enzyme, (b) conversion to a transiently inhibited species, and (c) conversion to an irreversibly inactive form. The amino acid composition of the chromophoric peptide obtained from the enzyme inactivated by either of the compounds was consistent with the occurrence of an initial acylation of serine-70 of the protein.