Investigating the structural influence of surface mutations on acetylcholinesterase inhibition by organophosphorus compounds and oxime reactivation


Kucukkilinc T. , Cochran R., Kalisiak J., Garcia E., Valle A., Amitai G., ...More

CHEMICO-BIOLOGICAL INTERACTIONS, vol.187, pp.238-240, 2010 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 187
  • Publication Date: 2010
  • Doi Number: 10.1016/j.cbi.2010.03.050
  • Title of Journal : CHEMICO-BIOLOGICAL INTERACTIONS
  • Page Numbers: pp.238-240

Abstract

Organophosphates (OPs) exert their toxicity by inhibiting primarily acetylcholinesterase (AChE) and to a lesser extent butyrylcholinesterase (BChE). Binary mixtures of mammalian AChE and oximes of varying structure have been recently considered for treatment of OP poisoning as catalytic bioscavengers. In this study wild type human AChE and human AChE with residue mutations D134H, D134H_E202Q and D134H_F338A were characterized and investigated for inhibition by OPs and consequent oxime reactivation of phosphylated enzymes. The rationale for selecting these substitution positions was based on D134H being a naturally occurring single nucleotide polymorphism (SNP) in humans and that E202Q and F338A mutations slow aging of OP inhibited AChEs.