PXD033616-1

PXD033616 is an original dataset announced via ProteomeXchange.

Title	Druggable Serine Proteases of Leishmania by Activity‐Based Protein Profiling
Description	Leishmaniasis are a group of diseases caused by parasitic protozoa of the genus Leishmania. Current treatments are limited by difficult administration, high cost, poor efficacy, toxicity, and growing resistance. New agents, with new mechanisms of action, are urgently needed to treat the disease. Although extensively studied in other organisms, serine proteases (SPs) have not been widely explored as antileishmanial drug targets. Herein we report for the first time an activity-based protein profiling (ABPP) strategy to investigate new therapeutic targets within the SPs of the Leishmania parasites. Active site directed fluorophosphonate probes (rhodamine and biotin‐conjugated) were used for the detection and identification of active Leishmania serine hydrolases (SHs). Significant differences were observed in the SHs expression levels throughout the Leishmania life cycle and between different Leishmania species. Using iTRAQ-labelling-based quantitative proteomic mass spectrometry, we identified two targetable SPs in Leishmania mexicana: carboxypeptidase LmxM.18.0450 and prolyl oligopeptidase LmxM.36.6750. Druggability was ascertained by selective inhibition using the commercial serine protease inhibitors chymostatin, lactocystin and ZPP, which represent templates for future anti-leishmanial drug discovery programs. Collectively, the use of ABPP method complements existing genetic methods for target identification and validation in Leishmania.
HostingRepository	PRIDE
AnnounceDate	2022-07-04
AnnouncementXML	Submission_2022-07-04_02:46:08.329.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Karunakaran Kalesh
SpeciesList	scientific name: Leishmania mexicana; NCBI TaxID: 5665;
ModificationList	No PTMs are included in the dataset
Instrument	TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2022-05-04 10:07:15	ID requested
⏵ 1	2022-07-04 02:46:08	announced

Dataset with its publication pending

submitter keyword: Leishmania, Serine Protease, Activity-Based Protein Profiling

Karunakaran Kalesh
contact affiliation	School of Health and Life Sciences, Teesside University, UK
contact email	k.karunakaran@tees.ac.uk
lab head
Karunakaran Kalesh
contact affiliation	Teesside University
contact email	k.karunakaran@tees.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/2022/07/PXD033616

PRIDE project URI

• PRIDE
  1. PXD033616
     1. Label: PRIDE project
     2. Name: Druggable Serine Proteases of Leishmania by Activity‐Based Protein Profiling