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PXD031708-2

PXD031708 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleCompetitive Profiling of Ligandable Cysteines in Staphylococcus aureus with an Organogold Compound
DescriptionWith the idea of exploiting metal-templated reactions to achieve selective modification of cysteines in proteins for antibacterial applications, an organometallic cyclometalated Au(III) compound was explored in a competitive chemoproteomic approach based on the isoDTB-ABPP (isotopically labelled desthiobiotin azide-activity-based protein profiling) technology in S. aureus cell extracts. In this way, more than 100 ligandable cysteines where identified, of which 10 were close to functional sites of proteins encoded by essential genes indicating potential for antibiotic development. Interestingly, more than 50% of the identified ligandable sites were not engaged by organic alpha-chloroacetamides in a previous study, indicating that organometallic compounds expand the ligandable space in bacteria. A selected interaction identified by isoDTB-ABPP was validated using an enzyme activity assay, and intact protein mass spectrometry showed that cysteine arylation of an unprecedented target occurs with the studied compound. The obtained results constitute the proof-of-concept that this family of organogold compounds has potential for therapeutic protein targeting via selective, covalent modification of cysteine residues in bacteria. Looking more broadly, our study demonstrates that the targets of cyclometalated gold compounds can be studied proteome-wide with competitive residue-specific chemoproteomics enabling the expansion of the known ligandable proteome to sites that can be addressed with this compound class.
HostingRepositoryPRIDE
AnnounceDate2023-11-14
AnnouncementXMLSubmission_2023-11-14_08:55:38.653.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterStephan M. Hacker
SpeciesList scientific name: Staphylococcus aureus; NCBI TaxID: 1280;
ModificationListNo PTMs are included in the dataset
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-02-16 02:47:29ID requested
12022-04-19 06:55:55announced
22023-11-14 08:55:39announced2023-11-14: Updated project metadata.
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Covalent inhibitors, Organogold,Competitive residue-specific proteomics, Antibiotics
Contact List
Stephan Hacker
contact affiliationDepartment of Chemistry, Technical University of Munich, Lichtenbergstr. 4, 85748 Garching, Germany
contact emailstephan.m.hacker@tum.de
lab head
Stephan M. Hacker
contact affiliationTechnical University of Munich
contact emailstephan.m.hacker@tum.de
dataset submitter
Full Dataset Link List
Dataset FTP location
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