Inhibition of β-lactamase-I by 6-β-sulfonamidopenicillanic acid sulfones: Evidence for conformational change accompanying the inhibition process

A number of 6-β-sulfonamidopenicillanic acid sulfones were examined for their ability to inhibit Bacillus cereus$\text{569}\text{H}$ β-lactamase I. Among these, 6-β-trifluoromethane sulfonamidopenicillanic acid sulfone was found to be the most potent inhibitor, effecting rapid and irreversible inactivation of the enzyme. Optical rotatory dispersion and differential scanning calorimetry were employed to probe the possible conformational changes accompanying the inactivation of B. cereus$\text{569}\text{H}$ β-lactamase 1 by 6-β-trifluoromethane sulfonamidopenicillanic acid sulfone. Optical rotatory dispersion measurements indicated the presence of approximately 29 and 17% helical structure in the native and inactivated enzyme, respectively. Differential scanning calorimetry determinations revealed that the inactivated enzyme was less thermostable than the native β-lactamase. The temperatures of maximum heat absorption were 48.4(±0.5) and 57.4(±0.1)°C for the inactivated and the native enzyme, respectively. Extensive conformational changes accompanying the interaction of the enzyme with the inhibitor may be responsible for the irreversible loss in the catalytic activity.