PXD048457-1

PXD048457 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2024-01-11 05:31:46	ID requested
⏵ 1	2025-01-29 23:28:15	announced

10.1038/S41557-025-01745-8;

submitter keyword: Drug Target Screen, Chemoproteomics,Proton Pump Inhibitor, Rabeprazole

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

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/2025/01/PXD048457

PRIDE project URI

• PRIDE
  1. PXD048457
     1. Label: PRIDE project
     2. Name: Chemoproteomic screen to identify rabeprazole off-targets in intact HEK293 MSR cells