Design and expression of organiphosphorus acid anhydride hydrolase activity in human butyrylcholinesterase

An imidazolium ion is appropriately positioned in the oxyanion hole to catalyze spontaneous enzyme dephosphonylation, thus conferring a novel organophosphorus (OP) acid anhydride hydrolase activity upon butyrylcholinesterase (BuChE). This was the conclusion reached after the modeling of BuChE and identification of several locations near the active site Ser O(gamma) where catalysis may occur. A number of residues predicted to be near the active site and the oxyanion hole of human BuChE for mutation to His (G115H, G117H, Q119H and G121H) were selected and analyzed. One mutant, BuChE G117H, was found to be an active cholinesterase that also catalyzes hydrolysis of the OP nerve agents GB (sarin) and VX.