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  • Title: Interaction of tazobactam with Staphylococcus aureus PC1 beta-lactamase: a molecular modelling and enzyme kinetics study.
    Author: Denny BJ, Toomer CA, Lambert PA.
    Journal: Microbios; 1994; 78(317):245-57. PubMed ID: 8078414.
    Abstract:
    Tazobactam is a highly potent inhibitor of beta-lactamases. A kinetic study of its interaction with the class A Staphylococcus aureus PC1 beta-lactamase was undertaken which showed competitive inhibition with the substrate nitrocefin. When the enzyme was preincubated with inhibitor for varying lengths of time, the kinetic profile was consistent with a portion of the enzyme being irreversibly inactivated. Using the crystal 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 was crosslinked via a fragment of tazobactam to Lys-73. Trypsin digest experiments supported the proposed crosslinking reaction.
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