title: Review of tyrosine and lysine as new motifs for organophosphate binding to proteins that have no active site serine.
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.
authors.affiliation: Eppley Institute, 985950 University of Nebraska Medical Center, Omaha, NE 68198-5950, United States. olockrid@unmc.edu
authors.forename: Oksana
authors.initials: O
authors.lastname: Lockridge
authors.forename: Lawrence M
authors.initials: LM
authors.lastname: Schopfer
mesh_terms: D000818:Animals; D020134:Catalytic Domain; D006801:Humans; D006867:Hydrolases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism*; D010755:Organophosphates / Q000378:metabolism* / Q000633:toxicity; D011485:Protein Binding; D014443:Tyrosine / Q000378:metabolism*
chemical_list: D010755:Organophosphates; D014443:Tyrosine; D006867:Hydrolases; D008239:Lysine