Mechanistic support for the stepwise process for inactivation of class A β-lactamases by clavulanate

We proposed recently a stepwise process for the inactivation chemistry of class A β-lactamases by clavulanate (J. Am. Chem. Soc.1993, 115, 4435). A requisite protonation by an active-site water molecule was suggested to be a critical chemical step in enzyme inactivation. The details of this proposed stepwise mechanism have been explored further by three synthetic analogues of clavulanate.