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PXD041314-1

PXD041314 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleAssigning functionality to cysteines by base editing of cancer dependency genes
Description  Covalent chemistry represents an attractive strategy for expanding the ligandability of the proteome, and chemical proteomics has revealed numerous electrophile-reactive cysteines on diverse human proteins. Determining which of these covalent binding events impact protein function, however, remains challenging. Here, we describe a base-editing strategy to infer the functionality of cysteines by quantifying the impact of their missense mutation on cancer cell proliferation. The resulting atlas, which covers >13,800 cysteines on >1,750 cancer dependency proteins, confirms the essentiality of cysteines targeted by covalent drugs and, when integrated with chemical proteomic data, identifies essential, ligandable cysteines in >110 cancer dependency proteins. We further show that a stereoselective and site-specific ligand targeting an essential cysteine in TOE1 inhibits the nuclease activity of this protein through an apparent allosteric mechanism. Our findings thus describe a versatile method and valuable resource to prioritize the pursuit of small-molecule probes with high function-perturbing potential.
HostingRepositoryPRIDE
AnnounceDate2023-09-06
AnnouncementXMLSubmission_2023-09-06_09:41:46.910.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterHaoxinLi
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentOrbitrap Fusion
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-04-03 14:48:10ID requested
12023-09-06 09:41:47announced
22023-11-14 07:51:30announced2023-11-14: Updated project metadata.
Publication List
Keyword List
submitter keyword: ABPP, cysteine, base editing,covalent probe
Contact List
BenjaminCravatt
contact affiliationThe Scripps Research Institute
contact emailcravatt@scripps.edu
lab head
HaoxinLi
contact affiliationThe Scripps Research Institute
contact emailhaoxinli@scripps.edu
dataset submitter
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Dataset FTP location
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PRIDE project URI
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