PXD031708

PXD031708 is an original dataset announced via ProteomeXchange.

Title	Competitive Profiling of Ligandable Cysteines in Staphylococcus aureus with an Organogold Compound
Description	With 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.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:55:38.653.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Stephan M. Hacker
SpeciesList	scientific name: Staphylococcus aureus; NCBI TaxID: 1280;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2022-02-16 02:47:29	ID requested
1	2022-04-19 06:55:55	announced
⏵ 2	2023-11-14 08:55:39	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: Covalent inhibitors, Organogold,Competitive residue-specific proteomics, Antibiotics

Stephan Hacker
contact affiliation	Department of Chemistry, Technical University of Munich, Lichtenbergstr. 4, 85748 Garching, Germany
contact email	stephan.m.hacker@tum.de
lab head
Stephan M. Hacker
contact affiliation	Technical University of Munich
contact email	stephan.m.hacker@tum.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/2022/04/PXD031708

PRIDE project URI

• PRIDE
  1. PXD031708
     1. Label: PRIDE project
     2. Name: Competitive Profiling of Ligandable Cysteines in Staphylococcus aureus with an Organogold Compound