Review of tyrosine and lysine as new motifs for organophosphate binding to proteins that have no active site serine

Research output: Contribution to journalReview article

41 Scopus citations

Abstract

The accepted target for organophosphorus agent (OP) binding to enzymes is the active site serine in the consensus sequence Gly X Ser X Gly. New motifs have been identified by using mass spectrometry to fragment OP-labeled peptides. It has been found that OP can make covalent bonds with tyrosine and lysine in proteins that have no active site serine. The OP-tyrosine bond is stable, and does not undergo the decay seen with OP-serine. Information on OP binding to tyrosine has been applied to diagnosis of OP exposure, through the use of mass spectrometry to detect OP-labeled albumin in human and animal plasma. It is expected that the new OP binding motif will aid in the search for a mechanism of low dose OP toxicity. It is hypothesized that proteins involved in axonal transport, especially proteins whose function depends on reversible phosphorylation, are prime candidates for a role in OP-induced neurodegeneration. Treatment of neurodegenerative disorders could be developed by identifying methods to reverse OP binding to tyrosine.

Original languageEnglish (US)
Pages (from-to)344-348
Number of pages5
JournalChemico-Biological Interactions
Volume187
Issue number1-3
DOIs
StatePublished - Sep 2010

Keywords

  • Lysine
  • Nerve agents
  • Organophosphorus agents
  • Pesticides
  • Tyrosine

ASJC Scopus subject areas

  • Toxicology

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