PXD042307 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Direct mapping of ligandable tyrosines and lysines in cells with chiral sulfonyl fluoride probes |
Description | Advances in chemoproteomic technology have revealed covalent interactions between small molecules and protein nucleophiles, primarily cysteine, on a proteome-wide scale. Most chemoproteomic screening approaches are indirect, relying on competition between electrophilic fragments and a minimalist electrophilic probe with inherently limited proteome coverage. Here, we develop a chemoproteomic platform for direct electrophile-site identification based on enantiomeric pairs of clickable arylsulfonyl fluoride probes. Using stereoselective site modification as a proxy for ligandability in intact cells, we identified 634 tyrosines and lysines within functionally diverse protein sites, liganded by structurally diverse probes. Among multiple validated sites, we discovered a chiral probe that modifies Y228 in the MYC binding site of the epigenetic regulator WDR5, as revealed by a high-resolution crystal structure. A distinct chiral probe stimulates tumor cell phagocytosis by covalently modifying Y387 in the recently discovered immuno-oncology target, APMAP. Our work provides a deep resource of ligandable tyrosines and lysines for the development of covalent chemical probes. |
HostingRepository | PRIDE |
AnnounceDate | 2023-05-18 |
AnnouncementXML | Submission_2023-05-17_19:30:31.157.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | YingChen |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | TMT6plex-126 reporter+balance reagent acylated residue |
Instrument | Orbitrap Eclipse |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-05-17 19:00:29 | ID requested | |
⏵ 1 | 2023-05-17 19:30:31 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: Human, Eclipse, TMT |
Contact List
JackTaunton |
contact affiliation | Department of Cellular and Molecular Pharmacology, University of California, San Francisco |
contact email | jack.taunton@ucsf.edu |
lab head | |
YingChen |
contact affiliation | UCSF |
contact email | ying.chen@ucsf.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD042307
- Label: PRIDE project
- Name: Direct mapping of ligandable tyrosines and lysines in cells with chiral sulfonyl fluoride probes