Mass Spectrometry to Identify New Biomarkers of Nerve Agent Exposure
Abstract
Organophosphorus esters (OP) are known to make a covalent bond with the active site serine in the consensus sequence GXSXG of esterases and proteases. However, the site of attachment to proteins that have no active site serine is unknown. Human plasma as well as pure albumin, transferrin, tubulin, and synthetic peptides were treated with soman, sarin, DFP, chlorpyrifos oxon, dichlorvos, and FP-biotin. The site of covalent attachment of OP was determined by fragmentation in the QTRAP mass spectrometer. It was found that OP made a covalent bond with tyrosine in every protein and synthetic peptide tested. The reactive tyrosines were near an arginine or lysine. OP-tyrosine adducts were stable and did not undergo aging. In conclusion, a new OP binding motif has been identified. Recognition of this new OP binding motif may lead to an explanation of noncholinergic effects of OP and of chronic illness from low dose exposure.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2008
- Accession Number
- ADA483399
Entities
People
- Oksana Lockridge
Organizations
- University of Nebraska Medical Center