PXD044792

PXD044792 is an original dataset announced via ProteomeXchange.

Dataset Summary

Title	Discovery of highly Potent and Selective Activity-Based Probes for the Deubiquitylating Enzyme USP30
Description	Ubiquitin-specific protease 30 (USP30) is a deubiquitylating enzyme (DUB) localized in the mitochondrial membrane, which is related to PINK1/Parkin-mediated mitophagy, pexophagy, BAX/BAK-dependent apoptosis, and IKKβ-USP30-ACLY-regulated lipogenesis/tumorigenesis. Mission therapeutics pointed their in-house screened MTX652 as USP30 inhibitor for Phase I clinical trial in early 2022. Activity-based probes (ABPs) provide a powerful tool for screen USP30 inhibitors. Here, we report the first small molecule ABPs (ABP 2 and ABP 4) for profiling activity of USP30. Through in-gel fluorescence, target-enrichment and proteomics analysis, we demonstrate that ABP 2 and ABP 4 selectively engage USP30 at nanomolar concentration for only 10 min incubation time in live cells. This cellular USP30-engagement is selectively depending on the catalytic cysteine of USP30. Interestingly, DESI1 and DESI2, the small ubiquitin-related modifier (SUMO) proteases, are also engaged by ABP 2 and ABP 4, providing the novel strategy for these probes as DESIs ABPs. We use proteomics analysis to identify the probes targeted proteins by DIA analysis.
HostingRepository	PRIDE
AnnounceDate	2024-05-22
AnnouncementXML	Submission_2024-05-22_02:09:32.045.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Fangyuan Cao
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Dataset History

Revision	Datetime	Status	ChangeLog Entry
0	2023-08-23 05:34:27	ID requested
⏵ 1	2024-05-22 02:09:32	announced

Publication List

10.1039/d4cb00029c;
Mondal M, Cao F, Conole D, Auner HW, Tate EW, Discovery of potent and selective activity-based probes (ABPs) for the deubiquitinating enzyme USP30. RSC Chem Biol, 5(5):439-446(2024) [pubmed]

10.1039/d4cb00029c;

Mondal M, Cao F, Conole D, Auner HW, Tate EW, Discovery of potent and selective activity-based probes (ABPs) for the deubiquitinating enzyme USP30. RSC Chem Biol, 5(5):439-446(2024) [pubmed]

Keyword List

submitter keyword: USP30
Activity-based probes
chemical probes
DESI
deubiquitinase.

submitter keyword: USP30

Activity-based probes

chemical probes

DESI

deubiquitinase.

Contact List

Ed Tate
contact affiliation	Imperial College London
contact email	e.tate@imperial.ac.uk
lab head
Fangyuan Cao
contact affiliation	Imperial College London
contact email	f.cao@imperial.ac.uk
dataset submitter

Full Dataset Link List

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PRIDE project URI

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/2024/05/PXD044792

PRIDE project URI

Repository Record List

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