Unprecedented Alkylation of the Catalytic Histidine in the Aging of Cholinesterases after Inhibition by Organophosphorus Pesticides.

Organophosphorus (OP) compounds pose a serious risk to human health by covalently modifying acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Currently approved oxime therapeutics can reactivate OP-inhibited AChE and BChE, despite significant limitations. The OP-inhibited enzymes undergo a secondary -dealkylation event, known as aging, for which no currently approved therapeutics are effective as treatments.