Biomarkers of exposure to organophosphorus poisons

A new motif for covalent binding to tyrosine in proteins that have no active site serine

Research output: Chapter in Book/Report/Conference proceedingChapter

4 Citations (Scopus)

Abstract

A new motif for Organophosphorus (OP) binding to tyrosine has been identified. Almost all proteins appear to be capable of binding OP covalently on tyrosine. Whether or not OP will bind to tyrosine in vivo will depend on the concentration of the protein, the concentration of the OP, and the ionization status of the tyrosine hydroxyl group. The latter factor appears to be dependent on the presence of nearby positively charged residues. The importance of the first and third factors is amply demonstrated in the case of albumin. The concentration of albumin is so high that albumin binds OP even though its rate of reaction is slow. The reaction of albumin's most sensitive tyrosine is aided by the presence of three positively charged residues within a five-residue stretch surrounding that tyrosine. Identification of new biomarkers of OP exposure may also lead to an understanding of why some people are intoxicated by low doses of OP that have no effect on the majority of the population. The new motif for OP binding to tyrosine may lead to new antidotes for OP poisoning; for example, peptides containing several tyrosines and several arginines may be effective OP scavengers.

Original languageEnglish (US)
Title of host publicationHandbook of Toxicology of Chemical Warfare Agents
PublisherElsevier Inc.
Pages847-858
Number of pages12
ISBN (Print)9780123744845
DOIs
StatePublished - Dec 1 2009

Fingerprint

Poisons
Serine
Tyrosine
Catalytic Domain
Biomarkers
Albumins
Proteins
Organophosphate Poisoning
Antidotes
Hydroxyl Radical
Arginine
Peptides
Population

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Biomarkers of exposure to organophosphorus poisons : A new motif for covalent binding to tyrosine in proteins that have no active site serine. / Lockridge, Oksana; Schopfer, Lawrence M; Masson, Patrick.

Handbook of Toxicology of Chemical Warfare Agents. Elsevier Inc., 2009. p. 847-858.

Research output: Chapter in Book/Report/Conference proceedingChapter

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