Biomarkers of Exposure to Organophosphorus Poisons: A New Motif for Covalent Binding to Tyrosine in Proteins That Have No Active Site Serine. A New Motif for Covalent Binding to Tyrosine in Proteins That Have No Active Site Serine

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are not the only protein targets of organophosphorus (OP) agent exposure in humans. Doses too low to inhibit AChE are neurotoxic to some humans, suggesting that other proteins are also modified. Mass spectrometry (MS) analysis shows that tyrosine in purified proteins and small synthetic peptides creates stable covalent bonds with OP compounds. A new, tyrosine-based motif for OP agent binding to proteins is proposed. An example of this motif is the binding of OP agents to albumin at tyrosine 411. MS has detected albumin adducts in humans who deliberately poisoned themselves with dichlorvos or chlorpyrifos. Antibodies to OP adducts on tyrosine are expected to be useful for detecting exposure and for identifying new biomarkers of exposure.

Original languageEnglish (US)
Title of host publicationHandbook of Toxicology of Chemical Warfare Agents
Subtitle of host publicationSecond Edition
PublisherElsevier Inc.
Pages953-965
Number of pages13
ISBN (Print)9780128001592
DOIs
StatePublished - Jan 21 2015

Fingerprint

Poisons
Serine
Tyrosine
Catalytic Domain
Biomarkers
Acetylcholinesterase
Albumins
Mass Spectrometry
Proteins
Dichlorvos
Organophosphorus Compounds
Butyrylcholinesterase
Chlorpyrifos
Carrier Proteins
Peptides
Antibodies

Keywords

  • Aging
  • Albumin
  • Biomarkers
  • Chemical warfare agents
  • Chlorpyrifos
  • Dichlorvos
  • Mass spectrometry
  • Nerve agents

ASJC Scopus subject areas

  • Medicine(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. 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: Second Edition. Elsevier Inc., 2015. p. 953-965.

Research output: Chapter in Book/Report/Conference proceedingChapter

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abstract = "Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are not the only protein targets of organophosphorus (OP) agent exposure in humans. Doses too low to inhibit AChE are neurotoxic to some humans, suggesting that other proteins are also modified. Mass spectrometry (MS) analysis shows that tyrosine in purified proteins and small synthetic peptides creates stable covalent bonds with OP compounds. A new, tyrosine-based motif for OP agent binding to proteins is proposed. An example of this motif is the binding of OP agents to albumin at tyrosine 411. MS has detected albumin adducts in humans who deliberately poisoned themselves with dichlorvos or chlorpyrifos. Antibodies to OP adducts on tyrosine are expected to be useful for detecting exposure and for identifying new biomarkers of exposure.",
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