PXD041185-1

PXD041185 is an original dataset announced via ProteomeXchange.

Title	Proteomic data and structure analysis combined reveal interplay of structural rigidity and flexibility on selectivity of cysteine cathepsins
Description	Addressing the elusive specificity of cysteine cathepsins, which in contrast to caspases and trypsin-like proteases lack strict specificity determining P1 pocket, was calling for innovative approaches. Proteomic analysis of cell lysates with human cathepsins K, V, B, L, S, and F identified 30,000 cleavage sites, which were analyzed by software platform SAPS-ESI (Statistical Approach to Peptidyl Substrate-Enzyme Specific Interactions). SAPS-ESI was used to generate clusters and training sets for support vector machine learning. Cleavage site predictions on the SARS-CoV-2 S protein, confirmed experimentally, exposed the most probable first cut under physiological conditions and suggested furin-like behavior of cathepsins. Crystal structure analysis of representative peptides in complex with cathepsin V revealed rigid and flexible sites consistent with analysis of proteomics data by SAPS-ESI that correspond to positions with heterogeneous and homogeneous distribution of residues. Thereby support for design of selective cleavable linkers of drug conjugates and drug discovery studies is provided.
HostingRepository	PRIDE
AnnounceDate	2024-10-07
AnnouncementXML	Submission_2024-10-07_13:49:08.733.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD041185
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	An Staes
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	alpha-amino acetylated residue; (R)-5-oxo-1,4-tetrahydrothiazine-3-carboxylic acid; 2-pyrrolidone-5-carboxylic acid (Gln); 3x(2)H labeled N6-acetyl-L-lysine; monohydroxylated residue; 6x(13)C labeled L-arginine; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos; LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2023-03-29 05:50:15	ID requested
⏵ 1	2024-10-07 13:49:09	announced

10.6019/PXD041185;

submitter keyword: iMixPro,COFRADIC, N-terminomics, cathepsins

Dusan Turk
contact affiliation	Jožef Stefan Institute, Department of Biochemistry and Molecular and Structural Biology, Jamova cesta 39, 1000 Ljubljana, Slovenia Centre of Excellence for Integrated Approaches in Chemistry and Biology of Proteins (CIPKeBiP), Jamova cesta 39, 1000 Ljubljana, Slovenia
contact email	dusan.turk@ijs.si
lab head
An Staes
contact affiliation	Medical Protein Chemistry
contact email	an.staes@vib-ugent.be
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/2023/03/PXD041185

PRIDE project URI

• PRIDE
  1. PXD041185
     1. Label: PRIDE project
     2. Name: Proteomic data and structure analysis combined reveal interplay of structural rigidity and flexibility on selectivity of cysteine cathepsins