PXD015104

PXD015104 is an original dataset announced via ProteomeXchange.

Title	Expedited mapping of the ligandable proteome using fully functionalized enantiomeric probe pairs
Description	A fundamental challenge in chemical biology and medicine is to understand and expand the fraction of the human proteome that can be targeted by small molecules. We recently described a strategy that integrates fragment-based ligand discovery with chemical proteomics to furnish global portraits of reversible small molecule-protein interactions in human cells. Excavating clear structure-activity relationships from these “ligandability” maps, however, was confounded by the distinct physicochemical properties and corresponding overall protein-binding potential of individual fragments. Here, we describe a compelling solution to this problem by introducing a next-generation set of fully functionalized fragments (FFFs) differing only in absolute stereochemistry. Using these enantiomeric probe pairs, or “enantioprobes”, we identify numerous stereoselective protein-fragment interactions in cells and show that these interactions occur at functional sites on proteins from diverse classes. Our findings thus indicate that incorporating chirality into FFF libraries provides a robust and streamlined method to discover ligandable proteins in cells.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:57:26.815.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yujia Wang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos; Orbitrap Fusion; LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2019-08-21 01:01:41	ID requested
1	2019-10-29 04:56:03	announced
2	2019-11-08 00:39:53	announced	2019-11-08: Updated publication reference for PubMed record(s): 31659311.
⏵ 3	2024-10-22 04:57:29	announced	2024-10-22: Updated project metadata.

Wang Y, Dix MM, Bianco G, Remsberg JR, Lee HY, Kalocsay M, Gygi SP, Forli S, Vite G, Lawrence RM, Parker CG, Cravatt BF, Expedited mapping of the ligandable proteome using fully functionalized enantiomeric probe pairs. Nat Chem, 11(12):1113-1123(2019) [pubmed]

10.1038/s41557-019-0351-5;

submitter keyword: Human, PBMCs, HEK293T, LC-MS/MS

Benjamin F. Cravatt
contact affiliation	Department of Chemistry The Scripps Research Institute
contact email	cravatt@scripps.edu
lab head
Yujia Wang
contact affiliation	The Scripps Research Institute
contact email	yujia@scripps.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/10/PXD015104

PRIDE project URI

• PRIDE
  1. PXD015104
     1. Label: PRIDE project
     2. Name: Expedited mapping of the ligandable proteome using fully functionalized enantiomeric probe pairs