Penicillanic acid sulfone: interaction with RTEM .beta.-lactamase from Escherichia coli at different pH values

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Abstract
The interaction of the sulfone of penicillanic acid with the TEM-2 .beta.-lactamase from E. coli was investigated as a function of pH between pH 7.0 and 9.6. The first-formed acyl-enzyme suffers 1 of 3 fates: deacylation, tautomerization to a bound enamine that transiently inhibits the enzyme, and a process (possibly transimination) that leads to enzyme inactivation. The observed changes in UV absorbance are consistent with the initially observed product of deacylation being the enamine tautomer of the imine from malonsemialdehyde and penicillamine sulfonate. The same enamine can be generated nonenzymically from the sulfone at high pH. The transiently inhibited enzyme appears to be the same anamine attached to the enzyme by an ester linkage. The rather complex kinetic behavior can be deconvoluted by exploiting the effect of pH on the partitioning of the acyl-enzyme between deacylation and the transiently inhibited form of the enzyme. The pathways followed by penicillanic acid sulfone provide a model for the behavior of a number of other reagents that inactivate the .beta.-lactamase.