Summary of project PR001740

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench,, where it has been assigned Project ID PR001740. The data can be accessed directly via it's Project DOI: 10.21228/M8SQ7X This work is supported by NIH grant, U2C- DK119886.


Project ID: PR001740
Project DOI:doi: 10.21228/M8SQ7X
Project Title:Chemoproteomics validates selective targeting of Plasmodium M1 alanyl aminopeptidase as a cross-species strategy to treat malaria
Project Summary:All current treatments for malaria are threatened by drug resistance, and new drug candidates that act on novel pathways are urgently needed. Here, we describe MIPS2673, a selective inhibitor of the Plasmodium M1 alanyl metalloaminopeptidase, which displays excellent in vitro antimalarial activity with no significant host cell toxicity. Biochemical assays revealed potent inhibition of recombinant Plasmodium falciparum (PfA-M1) and Plasmodium vivax (Pv-M1) M1 metalloaminopeptidases, with selectivity over other Plasmodium and human aminopeptidases. Orthogonal chemoproteomic methods based on thermal stability and limited proteolysis reproducibly identified PfA-M1 as the sole target of MIPS2673 in parasites from approximately 2,000 detected proteins. Furthermore, the limited proteolysis approach enabled estimation of the binding site on PfA-M1 to within ~5 Å of that determined by X-ray crystallography. Functional investigation by untargeted metabolomics further demonstrated that MIPS2673 inhibits the key role of PfA-M1 in haemoglobin digestion. Combined, our proteomics and metabolomics target deconvolution strategies provided unbiased confirmation of the on-target activity of a PfA-M1 inhibitor, and validated selective inhibition of this enzyme as a promising multi-stage and cross-species antimalarial strategy.
Institute:Monash University
Last Name:Siddiqui
First Name:Ghizal
Address:381 Royal Parade, Parkville, Melbourne, Victoria, 3052, Australia

Summary of all studies in project PR001740

Study IDStudy TitleSpeciesInstituteAnalysis
(* : Contains Untargted data)
(* : Contains raw data)
ST002792 Chemoproteomics validates selective targeting of Plasmodium M1 alanyl aminopeptidase as a cross-species strategy to treat malaria Plasmodium falciparum Monash University MS 2023-08-10 1 13 Uploaded data (1.5G)*