Penicillanic acid sulfone: nature of irreversible inactivation of the RTEM .beta.-lactamase from Escherichia coli

Abstract

When penicillanic acid sulfone in large molar excess is incubated with the RTEM .beta.-lactamase, the enzyme becomes inactivated irreversibly. From studies of the consequential spectroscopic changes, from the use of specifically tritiated penicillanic acid sulfone, and from comparison by isoelectric focusing of the enzyme after inactivation by the sulfone and by clavulanic acid, the inactivated enzyme appears to be cross-linked by a .beta.-aminoacrylate fragment deriving from C-5, C-6 and C-7 of the original .beta.-lactam. Model studies on the behavior of alcoholic solutions of penicillanic acid sulfone in the presence of amines are entirely consistent with this interpretation.