Summary of Study ST002108

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001335. The data can be accessed directly via it's Project DOI: 10.21228/M85416 This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST002108
Study TitleGenetic and chemical validation of Plasmodium falciparum aminopeptidase PfA-M17 as a drug target in the hemoglobin digestion pathway (Part 3)
Study SummaryPlasmodium 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.
Institute
Monash University
Last NameSiddiqui
First NameGhizal
Address381 Royal Parade, Parkville, Melbourne, Victoria, 3052, Australia
Emailghizal.siddiqui@monash.edu
Phone99039282
Submit Date2022-03-17
Raw Data AvailableYes
Raw Data File Type(s)raw(Thermo)
Analysis Type DetailLC-MS
Release Date2022-04-04
Release Version1
Ghizal Siddiqui Ghizal Siddiqui
https://dx.doi.org/10.21228/M85416
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Combined analysis:

Analysis ID AN003448 AN003449
Analysis type MS MS
Chromatography type HILIC HILIC
Chromatography system Thermo Dionex Ultimate 3000 RS Thermo Dionex Ultimate 3000 RS
Column ZIC-pHILIC (150 x 4.6mm,5um) equipped with a guard (SeQuant,Merck) ZIC-pHILIC (150 x 4.6mm,5um) equipped with a guard (SeQuant,Merck)
MS Type ESI ESI
MS instrument type Orbitrap Orbitrap
MS instrument name Thermo Q Exactive Orbitrap Thermo Q Exactive Orbitrap
Ion Mode POSITIVE NEGATIVE
Units relative intensity relative intensity

Chromatography:

Chromatography ID:CH002547
Instrument Name:Thermo Dionex Ultimate 3000 RS
Column Name:ZIC-pHILIC (150 x 4.6mm,5um) equipped with a guard (SeQuant,Merck)
Chromatography Type:HILIC
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