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 language | English (US) |
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Pages (from-to) | 344-348 |
Number of pages | 5 |
Journal | Chemico-Biological Interactions |
Volume | 187 |
Issue number | 1-3 |
DOIs | |
State | Published - Sep 2010 |
Keywords
- Lysine
- Nerve agents
- Organophosphorus agents
- Pesticides
- Tyrosine
ASJC Scopus subject areas
- Toxicology