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PXD043873

PXD043873 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleA General Approach for Activity-based Protein Profiling of Oxidoreductases with Redox-differentiated Diarylhalonium Warheads
DescriptionActivity-based protein profiling (ABPP) is a unique proteomic tool for measuring the activity of enzymes in their cellular context, which has been well established for enzyme classes exhibiting a characteristic nucleophilic residue (e.g. hydrolases). In contrast, the enzyme class of oxidoreductases has received less attention, as its members rely mainly on cofactors instead of nucleophilic amino acid residues for catalysis. ABPP probes have been designed for specific oxidoreductase subclasses, which rely on the oxidative conversion of the probes into strong electrophiles. Here we describe the development of ABPP probes for the simultaneous labeling of various subclasses of oxidoreductases. The probe warheads are based on hypervalent diarylhalonium salts, which show unique reactivity as their activation proceeds via a reductive mechanism resulting in aryl radicals leading to covalent labeling of liver proteins at several different amino acids in close proximity to the active sites. The redox potential of the probes can be tuned by isosteric replacement varyring the halonium central atom. ABPP experiments with liver using 16 probes differing in warhead, linker, and structure revealed distinct overlapping profiles and broad substrate specificities of several probes. With their capability of multi oxidoreductase subclass labeling – including rare examples for the class of reductases – and their unique design, the herein reported probes offer new opportunities for the investigation of the “oxidoreductome” of microorganisms, plants, animal and human tissues.
HostingRepositoryPRIDE
AnnounceDate2025-05-06
AnnouncementXMLSubmission_2025-05-06_12:54:37.225.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterLaura Liesinger
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListmonohydroxylated residue
InstrumenttimsTOF Pro
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-07-18 12:56:23ID requested
12025-05-06 12:54:39announced
Publication List
Krammer L, Darnhofer B, Kljajic M, Liesinger L, Schittmayer M, Neshchadin D, Gescheidt G, Kollau A, Mayer B, Fischer RC, Wallner S, Macheroux P, Birner-Gruenberger R, Breinbauer R, A general approach for activity-based protein profiling of oxidoreductases with redox-differentiated diarylhalonium warheads. Chem Sci, 16(15):6240-6256(2025) [pubmed]
10.1039/d4sc08454c;
Keyword List
submitter keyword: Oxidoreductase probe, mouse liver;,Activity-based Protein Profiling
Contact List
Ruth Birner-Gruenberger
contact affiliationInstitute of Chemical Technologies and Analytics, Technische Universität Wien, Getreidemarkt 9, 1060 Vienna, Austria; Research and Diagnostic Institute of Pathology, Medical University of Graz, Stiftingtalstraße 6, 8036, Graz, Austria
contact emailruth.birner-gruenberger@tuwien.ac.at
lab head
Laura Liesinger
contact affiliationFaculty of Technical Chemistry, Institute of Chemical Technologies and Analytics, Technische Universität Wien (TU Wien), 1060 Vienna, Austria;
contact emaillaura.liesinger@tuwien.ac.at
dataset submitter
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Dataset FTP location
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