Journal
CHEMICO-BIOLOGICAL INTERACTIONS
Volume 187, Issue 1-3, Pages 344-348Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.cbi.2010.03.002
Keywords
Pesticides; Nerve agents; Organophosphorus agents; Tyrosine; Lysine
Funding
- NCI NIH HHS [P30CA36727, P30 CA036727] Funding Source: Medline
- NINDS NIH HHS [U01 NS058056-03, U01 NS058056] Funding Source: Medline
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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 fora role in OP-induced neurodegeneration. Treatment of neurodegenerative disorders could be developed by identifying methods to reverse OP binding to tyrosine. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
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