# name
Chlorpyrifos oxon activates glutamate and lysine for protein cross-linking

# metadata.dc.description.abstract[].value
Chronic low-dose exposure to organophosphorus (OP) toxicants is correlated with an increase in the risk of impaired cognition and neurodegenerative diseases. A mechanism to explain this relationship is needed. We suggest that the formation of organophosphate-induced high-molecular-weight protein aggregates that disrupt cell function may be the missing link. It has been demonstrated that such aggregation can be promoted by OP-labeled lysine. Alternatively, OP-labeled glutamate may be the initiator. To test this hypothesis, we treated MAP-rich tubulin Sus scrofa and human transglutaminase with chlorpyrifos oxon. Trypsin-digested proteins were subjected to liquid chromatography−tandem mass spectrometry followed by Protein Prospector searches to identify diethyl phosphate adducts and cross-linked peptides. We report the presence of diethyl phosphate adducts on the side chains of glutamate, lysine, and tyrosine, as well as cross-links between glutamate and lysine. Glutamate-lysine cross-linking could be initiated either by diethyl phosphate-activated glutamate or by diethyl phosphate-activated lysine to form stable isopeptide bonds between and within proteins. It was concluded that organophosphate-induced high-molecular-weight protein aggregates could promote brain dysfunction.

# metadata.dc.relation.ispartof[].value
Chemical Research in Toxicology, 2023, vol. 36, num. 1, p. 112-121

# metadata.dc.rights[].value
cc by-nc-nd (c) Diego Muñoz-Torrero López-Ibarra, et al., 2023

# metadata.dc.source[].value
Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)

# metadata.dc.title[].value
Chlorpyrifos oxon activates glutamate and lysine for protein cross-linking