Endogenous structure of antimalarial target Pf ATP4 reveals new class of apicomplexan P-type ATPase modulators

抗疟靶标Pf ATP4的内源性结构揭示了一类新的顶复门P型ATPase调节剂

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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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