INTERACTION OF TAZOBACTAM WITH STAPHYLOCOCCUS-AUREUS PC1 BETA-LACTAMASE - A MOLECULAR MODELING AND ENZYME-KINETICS STUDY

Tazobactam is a highly potent inhibitor of beta-lactamases. A kinetic study of its interaction with the class A Staphylococcus aureus PC1 be ta-lactamase was undertaken which showed competitive inhibition with t he substrate nitrocefin. When the enzyme was preincubated with inhibit or for varying lengths of time, the kinetic profile was consistent wit h a portion of the enzyme being irreversibly inactivated. Using the cr ystal structure of the enzyme a molecular modelling study revealed the likely interactions of the inhibitor at the active site of the enzyme . It was shown that a possible reaction could occur in which Ser-70 wa s crosslinked via a fragment of tazobactam to Lys-73. Trypsin digest e xperiments supported the proposed crosslinking reaction.