PXD032358

PXD032358 is an original dataset announced via ProteomeXchange.

Title	Genetic and chemical validation of Plasmodium falciparum aminopeptidase PfA-M17 as a drug target in the hemoglobin digestion pathway
Description	Plasmodium falciparum, the causative agent of malaria, continues to remain a global health threat since these parasites are now resistant to all anti-malaria drugs used throughout the world. Accordingly, drugs with novel modes of action are desperately required to combat malaria. P. falciparum parasites infect human red blood cells where they digest the hosts main protein constituent, hemoglobin. Leucine aminopeptidase PfA-M17 is one of several aminopeptidases that have been implicated in the last step of this digestive pathway. Here we utilize both reverse genetics and a compound specifically designed to inhibit the activity of PfA-M17 to show that PfA-M17 is essential for P. falciparum survival as it provides parasites with free amino acids for growth, many of which are highly likely to originate from hemoglobin. We further show that our inhibitor is on-target for PfA-M17 and has the ability to kill parasites at nanomolar concentrations. Thus, in contrast to other hemoglobin-degrading proteases that have overlapping redundant functions, we validate PfA-M17 as a potential novel drug target.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:39:39.335.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ghizal Siddiqui
SpeciesList	scientific name: Plasmodium falciparum 365.1; NCBI TaxID: 1245018; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-03-17 04:22:09	ID requested
1	2022-09-12 02:47:38	announced
⏵ 2	2024-10-22 05:39:39	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: Plasmodium falciparum, PfA-M17, malaria, haemoglobin digestion

Tania de Koning-Ward
contact affiliation	School of Medicine, Deakin University, Geelong, 3216, Australia
contact email	taniad@deakin.edu.au
lab head
Ghizal Siddiqui
contact affiliation	Monash University
contact email	ghizal.siddiqui@monash.edu
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/2022/09/PXD032358

PRIDE project URI

• PRIDE
  1. PXD032358
     1. Label: PRIDE project
     2. Name: Genetic and chemical validation of Plasmodium falciparum aminopeptidase PfA-M17 as a drug target in the hemoglobin digestion pathway