PXD035891

PXD035891 is an original dataset announced via ProteomeXchange.

Title	Activity-Based Protein Profiling of Human and Plasmodium Serine Hydrolases and Interrogation of Potential Antimalarial Targets
Description	Malaria remains a global health issue requiring the identification of novel therapeutic targets to combat drug resistance. Metabolic serine hydrolases are druggable enzymes playing essential roles in lipid metabolism. However, very few have been investigated in malaria-causing parasites. Here, we used fluorophosphonate broad-spectrum activity-based probes and quantitative chemical proteomics to annotate and profile the activity of more than half of predicted serine hydrolases in P. falciparum across the erythrocytic cycle. Using conditional genetics, we show that the activities of four serine hydrolases, previously annotated as essential (or important) in genetic screens, are actually dispensable for parasite replication. Importantly, we also identified eight human serine hydrolases that are specifically activated at different developmental stages. Chemical inhibition of two of them blocks parasite replication. This strongly suggests that parasites co-opt the activity of host enzymes and opens a new drug development strategy against which the parasite is less likely to develop resistance.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:30:20.135.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Dara Davison
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606; scientific name: Plasmodium falciparum (isolate 3D7); NCBI TaxID: 36329;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-08-08 10:17:17	ID requested
1	2022-10-14 08:53:41	announced
⏵ 2	2023-11-14 08:30:22	announced	2023-11-14: Updated project metadata.

Davison D, Howell S, Snijders AP, Deu E, serine hydrolases and interrogation of potential antimalarial targets. iScience, 25(9):104996(2022) [pubmed]

submitter keyword: ABP, ABPP,Plasmodium falciparum, serine hydrolase, malaria, chemical proteomics, fluorophosphonate

Dr Dara Davison
contact affiliation	The Francis Crick Institute, London, NW1 1AT, United Kingdom
contact email	dara.davison@crick.ac.uk
lab head
Dara Davison
contact affiliation	UCL
contact email	d.davison@ucl.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/2022/10/PXD035891

PRIDE project URI

• PRIDE
  1. PXD035891
     1. Label: PRIDE project
     2. Name: Activity-Based Protein Profiling of Human and Plasmodium Serine Hydrolases and Interrogation of Potential Antimalarial Targets