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PXD066371-2

PXD066371 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleKetone Bodies-mediated Cysteine Modifications Discovered by Chemical Proteomics
DescriptionAll the studies of ketone body-dependent post-translational modifications (PTMs), notably those mediated by ketone bodies, β-hydroxybutyrate (Bhb) and acetoacetate (Acac), have focused on lysine acylations. However, given the chemically diverse and reactive nature of metabolites generated, it remains unclear whether non-lysine modifications can also happen. Here, we report the synthesis of an acetoacetate-alkyne (Acac-alkyne) chemical probe that enables efficient metabolic labeling, robust fluorescent visualization, and mass spectrometry-based identification of Acac-modified proteins. By combining chemical proteomics with open-search strategy, we showed that Acac will induce previously uncharacterized cysteine modifications in mammalian cells. Notably, cysteine S-crotonation (Ccr) is validated by employing both probe-based and standard peptide-based co-elution assays. Metabolic pathway tracing further identifies BDH1 and ECHS1 as key enzymes that generate Ccr formation. Together, these findings establish ketone metabolism as a novel source of cysteine modifications and provide an alternative mechanistic pathway to explain the profound biological effects of ketone body.
HostingRepositoryiProX
AnnounceDate2025-07-22
AnnouncementXMLSubmission_2026-02-02_23:11:59.488.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterYuanfei Zhou
SpeciesList scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationListiodoacetamide derivatized residue
InstrumentOrbitrap Exploris 240; Orbitrap Exploris 480
Dataset History
RevisionDatetimeStatusChangeLog Entry
02025-07-21 20:16:17ID requested
12025-07-21 20:16:39announced
22026-02-02 23:12:00announced2026-02-03: Add info.
Publication List
Zhou YF, Zhang L, Niu ZL, Wang X, Storper A, Hunt R, Zhao Y, Sharifi N, Wang ZA, Chemical Proteomics Identifies Ketogenesis-Mediated Cysteine Modifications Regulating Redox Function. Angew Chem Int Ed Engl, ():e19830(2026) [pubmed]
Keyword List
submitter keyword: Ketone Bodies, Cysteine Modifications, Chemical Proteomics
Contact List
Zhipeng Wang
contact affiliationDesai Sethi Urology Institute & Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine
contact emailzaw29@miami.edu
lab head
Yuanfei Zhou
contact affiliationDesai Sethi Urology Institute & Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine
contact emailyxz2215@miami.edu
dataset submitter
Full Dataset Link List
iProX dataset URI