PXD004112

PXD004112 is an original dataset announced via ProteomeXchange.

Title	Defining the landscape of EPHA2 Inhibition by Clinical Kinase Inhibitors
Description	The receptor tyrosine kinase EPHA2 plays important roles in oncogenesis, metastasis and treatment resistance but therapeutic targeting, drug discovery or investigation of EPHA2 biology is hampered by the lack of appropriate inhibitors and structural information on how these interact with the protein. Here, we used chemical proteomics to survey 235 clinical kinase inhibitors and identified 24 with sub-micromolar potency for EPHA2. We generated nine high resolution co-crystal structures to identify drug-protein interactions at the atomic level. The combination of compound selectivity, structure determinantion and kinome-wide sequence alignment allowed us to develop a classification system in which amino acids in the drug binding site are categorized into key, scaffold, potency and selectivity residues. This scheme should be generally applicable in kinase drug discovery and we anticipate that the provided information will greatly facilitate the development of selective EPHA2 inhibitors in particular and the repurposing of clinical kinase inhibitors in general.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:28:50.083.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Stephanie Wilhelm
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2016-05-09 00:29:48	ID requested
1	2017-01-03 03:22:50	announced
2	2017-10-24 03:37:08	announced	Updated project metadata.
⏵ 3	2024-10-22 04:28:50	announced	2024-10-22: Updated project metadata.

Heinzlmeir S, Kudlinzki D, Sreeramulu S, Klaeger S, Gande SL, Linhard V, Wilhelm M, Qiao H, Helm D, Ruprecht B, Saxena K, M, é, dard G, Schwalbe H, Kuster B, Chemical Proteomics and Structural Biology Define EPHA2 Inhibition by Clinical Kinase Drugs. ACS Chem Biol, 11(12):3400-3411(2016) [pubmed]

curator keyword: Biomedical

submitter keyword: EPHA2 co-crystals, selectivity profiling,chemical proteomics, residue categorization, drug protein interactions

Bernhard Kuster
contact affiliation	Chair of Proteomics and Bioanalytics, Technische Universität München, Germany
contact email	kuster@tum.de
lab head
Stephanie Wilhelm
contact affiliation	Chair of Proteomics and Bioanalytics, Technische Universität München, Germany
contact email	stephanie.heinzlmeir@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/2016/12/PXD004112

PRIDE project URI

• PRIDE
  1. PXD004112
     1. Label: PRIDE project
     2. Name: Defining the landscape of EPHA2 Inhibition by Clinical Kinase Inhibitors