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

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

CHEMICO-BIOLOGICAL INTERACTIONS, cilt.187, ss.238-240, 2010 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 187
  • Basım Tarihi: 2010
  • Doi Numarası: 10.1016/j.cbi.2010.03.050
  • Dergi Adı: CHEMICO-BIOLOGICAL INTERACTIONS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.238-240
  • Hacettepe Üniversitesi Adresli: Evet

Özet

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.