PXD042307

PXD042307 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2023-05-17 19:00:29	ID requested
⏵ 1	2023-05-17 19:30:31	announced

Dataset with its publication pending

submitter keyword: Human, Eclipse, TMT

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

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PRIDE project URI

• PRIDE
  1. PXD042307
     1. Label: PRIDE project
     2. Name: Direct mapping of ligandable tyrosines and lysines in cells with chiral sulfonyl fluoride probes