Penicillanic acid sulfone: an unexpected isotope effect in the interaction of 6.alpha.- and 6.beta.-monodeuterio and of 6,6-dideuterio derivatives with RTEM .beta.-lactamase from Escherichia coli. Crystal structure of penicillanic acid sulfone (original) (raw)

Penicillanic acid sulfone (1) is both a substrate and an inactivator of the RTEM 8-lactamase. About 7000 hydrolytic events occur before enzyme inactivation. The 6,6-dideuterio sulfone shows a 3-fold acceleration of both the hydrolysis reaction and the enzyme inactivation. The kinetic and spectroscopic results are nicely accommodated by a scheme in which a transiently stable intermediate is formed in an isotopically sensitive step. The deuterated material partitions less readily toward this transiently stable intermediate by virtue Abbreviations used: RTEM specifies the source of the plasmid [see Datta & Kontomichalou (1965)l; TEM-2 specifies the enzyme [see Sutcliffe (1978)j; DEAE, diethylaminoethyl; NADH, reduced nicotinamide adenine dinucleotide.