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PXD009444-3

PXD009444 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleA chemical probe to monitor parkinsonism-associated protein DJ-1 in live cells
DescriptionOxidative stress is a contingent trigger of Parkinson`s disease (PD). DJ-1, a protein involved in oxidative stress sensing, gained major attention when mutations in its gene were identified in PD patients. Although the study of the corresponding protein function is still in its infancy, a crucial oxidation sensor at a conserved cysteine was linked to the disease. Inspired by inhibition studies with a bacterial homolog of DJ-1 we here screen several amino-epoxycylcohexenones and identify a chemical probe that exhibits specificity for the human protein in various cell lines. The probe selectively labeled the oxidation sensor via nucleophilic attack of the conserved cysteine onto the epoxide ring. This covalent addition occurred only in the reduced state. Whole proteome studies in HeLa, A549 and SHSY5Y cell lines confirmed strong enrichment of solely reduced DJ-1 which was diminished by increasing oxidative stress. The probe thus facilitates the first selective in situ monitoring of DJ-1 in its reduced state and enables studying the function of this important biomarker in dependence of oxidative stress.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_04:44:30.479.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterJonas Drechsel
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList6x(13)C labeled residue; iodoacetamide derivatized residue
InstrumentLTQ Orbitrap XL; Orbitrap Fusion; Q Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02018-04-09 08:37:48ID requested
12018-07-17 01:43:02announced
22018-07-30 01:28:11announcedUpdated publication reference for PubMed record(s): 30011180.
32024-10-22 04:46:48announced2024-10-22: Updated project metadata.
Publication List
Drechsel J, Mandl FA, Sieber SA, Chemical Probe To Monitor the Parkinsonism-Associated Protein DJ-1 in Live Cells. ACS Chem Biol, 13(8):2016-2019(2018) [pubmed]
10.1021/acschembio.8b00633;
Keyword List
curator keyword: Biomedical
submitter keyword: Human, LC-MS/MS
Contact List
Stephan A Sieber
contact affiliationCenter for Integrated Protein Science Munich (CIPSM) at the Department of Chemistry, Technische Universität München, Lichtenbergstraße 4, 85747 Garching b. München ( lab head )
contact emailstephan.sieber@tum.de
lab head
Jonas Drechsel
contact affiliationTU Munich
contact emailjonas.drechsel@tum.de
dataset submitter
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Dataset FTP location
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PRIDE project URI
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