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Updated: May 23, 2025

Author Spotlight: Identifying Compensatory Pathways in Malaria Parasites Containing Hypomorphic Allele of Essential Protein Kinases
Published on: November 22, 2024
Endogenous structure of antimalarial target Pf ATP4 reveals new class of apicomplexan P-type ATPase modulators
Abstract:
The Plasmodium falciparum sodium efflux pump Pf ATP4 is a leading antimalarial target, but suffers from a lack of high-resolution structural information needed to identify functionally important features in conserved regions and guide rational design of next generation inhibitors. Here, we determine a 3.7Å cryoEM structure of Pf ATP4 purified from CRISPR-engineered P. falciparum parasites, revealing a previously unknown, apicomplexan-specific binding partner, Pf ABP, which forms a conserved, likely modulatory interaction with Pf ATP4. The discovery of Pf ABP presents a new avenue for designing novel Pf ATP4 inhibitors.
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