PXD048457 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Chemoproteomic screen to identify rabeprazole off-targets in intact HEK293 MSR cells |
Description | Proton pump inhibitors (PPIs) have become top-selling drugs worldwide. They are prodrugs activated by protonation in highly acidic environments. They inhibit stomach acid secretion by covalently modifying the gastric H+/K+-ATPase. However, little is known about alternative activation mechanisms and target proteins in non-acidic environments. Employing a chemoproteomic approach in living cells, we find rabeprazole to form covalent conjugates with numerous zinc-binding proteins. We show that one of the main target proteins, density-regulated protein (DENR), is conjugated to rabeprazole through a cysteine residue forming part of the zinc-binding site. We propose that zinc acts as a Lewis acid, obviating the need for low pH, to promote the activation of PPIs in non-acidic environments. Our findings may aid the understanding of secondary drug effects and/or the repurposing of PPIs. |
HostingRepository | PRIDE |
AnnounceDate | 2025-01-30 |
AnnouncementXML | Submission_2025-01-29_23:28:15.604.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Frank Stein |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | N-ethylmaleimide derivatized cysteine; iodoacetamide derivatized residue |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2024-01-11 05:31:46 | ID requested | |
⏵ 1 | 2025-01-29 23:28:15 | announced | |
Publication List
Keyword List
submitter keyword: Drug Target Screen, Chemoproteomics,Proton Pump Inhibitor, Rabeprazole |
Contact List
Tobias P Dick |
contact affiliation | Division of Redox Regulation, DKFZ-ZMBH Alliance, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany |
contact email | t.dick@dkfz.de |
lab head | |
Frank Stein |
contact affiliation | EMBL |
contact email | frank.stein@embl.de |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD048457
- Label: PRIDE project
- Name: Chemoproteomic screen to identify rabeprazole off-targets in intact HEK293 MSR cells