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PXD032358

PXD032358 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleGenetic and chemical validation of Plasmodium falciparum aminopeptidase PfA-M17 as a drug target in the hemoglobin digestion pathway
DescriptionPlasmodium 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.
HostingRepositoryPRIDE
AnnounceDate2022-09-12
AnnouncementXMLSubmission_2022-09-12_02:47:38.547.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterGhizal Siddiqui
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606; scientific name: Plasmodium falciparum 365.1; NCBI TaxID: 1245018;
ModificationListacetylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-03-17 04:22:09ID requested
12022-09-12 02:47:38announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Plasmodium falciparum, malaria, PfA-M17, haemoglobin digestion
Contact List
Tania de Koning-Ward
contact affiliationSchool of Medicine, Deakin University, Geelong, 3216, Australia
contact emailtaniad@deakin.edu.au
lab head
Ghizal Siddiqui
contact affiliationMonash University
contact emailghizal.siddiqui@monash.edu
dataset submitter
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Dataset FTP location
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PRIDE project URI
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