PXD034529

PXD034529 is an original dataset announced via ProteomeXchange.

Title	Organophosphorus pesticides catalyze protein crosslinking
Description	Exposure to organophosphorus pesticides (OP) can have chronic adverse effects that are independent of inhibition of acetylcholinesterase, the classic target for acute OP toxicity. In pure proteins, the organophosphorus pesticide chlorpyrifos oxon induces a crosslink between lysine and glutamate (or aspartate) with loss of water. Tubulin is particularly sensitive to OP-induced crosslinking. Our goal was to explore OP-induced crosslinking in a complex protein sample, MAP-rich tubulin from Sus scrofa, and to test 8 OP for their capacity to catalyze isopeptide crosslinking. We treated 100 µg of MAP-rich tubulin with 100 µM chlorpyrifos, chlorpyrifos oxon, methamidophos, paraoxon, diazinon, diazoxon, monocrotophos, or dichlorvos. Each sample was separated on SDS PAGE and stained with Coomassie blue. Five gel slices (at about 30, 50, 150, and 300 kDa, and the top of the separating gel) were removed from the lanes for each of the eight OP samples and from untreated control lanes. These gel slices were subjected to in-gel trypsin digestion. MSMS fragmentation spectra of the tryptic peptides were examined for isopeptide crosslinks. Sixteen spectra yielded convincing evidence for isopeptide crosslinked peptides. Ten were from the chlorpyrifos oxon reaction, 1 from dichlorvos, 1 from paraoxon, 1 from diazinon, and 3 from diazoxon. It was concluded that catalysis of protein crosslinking is a general property of organophosphorus pesticides and pesticide metabolites.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_07:36:33.734.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Lawrence Schopfer
SpeciesList	scientific name: Sus scrofa domesticus (domestic pig); NCBI TaxID: 9825;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-06-15 03:31:53	ID requested
1	2022-10-13 16:14:42	announced
⏵ 2	2023-11-14 07:36:34	announced	2023-11-14: Updated project metadata.

Schopfer LM, Onder S, Lockridge O, Organophosphorus Pesticides Promote Protein Cross-Linking. Chem Res Toxicol, 35(9):1570-1578(2022) [pubmed]

submitter keyword: chlorpyrifos oxon, Protein Prospector, MAP-rich tubulin,isopeptide, crosslinks

Oksana Lockridge
contact affiliation	Eppley Institute University of Nebraska Medical Center Omaha, Nebraska, USA
contact email	olockrid@unmc.edu
lab head
Lawrence Schopfer
contact affiliation	University of Nebraska Medical Center
contact email	lmschopf@unmc.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD034529
     1. Label: PRIDE project
     2. Name: Organophosphorus pesticides catalyze protein crosslinking