PXD057304

PXD057304 is an original dataset announced via ProteomeXchange.

Title	Covalent fragment screening to inhibit the E3 ligase activity of bacterial NEL enzymes SspH1 and SspH2
Description	As the global fight against antimicrobial resistance in bacteria becomes increasingly pressing, new tool compounds are needed to understand and identify novel therapeutic targets. Here, cysteine-directed fragment-based drug discovery is coupled with a high throughput chemistry direct-to-biology screening platform to target the catalytic cysteine of a family of bacterial effector proteins, the Novel E3 Ligases (NELs) from Salmonella and Shigella. These effector E3 ligases are particularly interesting as a potential drug target because they are injected into host cells during infection, have no human homologues and disrupt host immune response to infection. We successfully identify lead compounds against the SspH subfamily of NELs from Salmonella and show that these proteins are inhibited by compound treatment, representing an exciting starting point for development into specific and potent tool compounds.
HostingRepository	PRIDE
AnnounceDate	2025-11-10
AnnouncementXML	Submission_2025-11-09_19:50:20.259.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Aini Vuorinen
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	timsTOF Pro 2

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-29 11:54:37	ID requested
⏵ 1	2025-11-09 19:50:28	announced

10.1039/d5cb00177c;

Kennedy CR, McPhie KA, Vuorinen A, Dudley-Fraser J, Esposito D, Maslen S, McCarthy WJ, Pettinger J, Skehel JM, Bush J, House D, Rittinger K, Covalent fragment screening to inhibit the E3 ligase activity of bacterial NEL enzymes SspH1 and SspH2. RSC Chem Biol, 7(1):153-168(2026) [pubmed]

submitter keyword: Bacterial NELs, fragment-based drug discovery, covalent fragments, Salmonella effectors, chemoproteomics, E3 ligase, high throughput chemistry

Katrin Rittinger
contact affiliation	Molecular Structure of Cell Signalling Laboratory, The Francis Crick Institute, United Kingdom
contact email	katrin.rittinger@crick.ac.uk
lab head
Aini Vuorinen
contact affiliation	The Francis Crick Institute
contact email	aini.vuorinen@crick.ac.uk
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/2025/11/PXD057304

PRIDE project URI

• PRIDE
  1. PXD057304
     1. Label: PRIDE project
     2. Name: Covalent fragment screening to inhibit the E3 ligase activity of bacterial NEL enzymes SspH1 and SspH2