Increasing the Catalytic Efficiency of Butyrylcholinesterase through Surface Loop Modifications

Abstract

Organophosphorus compounds (OPs) are highly neurotoxic anticholinesterase agents. Their widespread availability and potency make them attractive for use in chemical terrorism and warfare. Developing safe and efficient methods for counteracting the effects of OP intoxication remains a priority. When given prophylactically, the G117H mutant of butyrylcholinesterase (BChEG117H) is able to catalytically hydrolyze OPs before they reach target organs. However, its widespread use as a treatment for OP intoxication is limited by several factors, including its extremely low substrate-turnover rate. To address this, we hypothesized structural changes to BChEG117H in the form of surface loop modifications would increase the enzyme’s catalytic efficiency. Data on butyrylthiocholine substrate hydrolysis is presented for BChEG117H and wild-type butyrylcholinesterase (BChE_wt).