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Eps15 homology domain-containing protein (PfEHD) is a dynamin-like ATPase in Plasmodium falciparum that plays a central role in endocytosis and vesicular trafficking. It is essential for the intra-erythrocytic development of the parasite, where it facilitates the uptake of host cell hemoglobin and the mobilization of lipids to the neutral lipid storage site near the food vacuole. PfEHD is a membrane-bound protein that associates with a dynamic vesicular network, mediating membrane remodeling and scission processes necessary for nutrient acquisition. While not the direct primary target of the novel antimalarial candidate MMV688533, mutations in PfEHD (such as D218Y) have been identified as mediators of low-grade resistance to this compound, highlighting its importance in the parasite's drug response pathways. As an essential protein with no direct human ortholog performing the same specialized role in the parasite's life cycle, PfEHD represents a promising target for the development of next-generation antimalarial therapeutics.
Inhibition of endocytosis and vesicular trafficking
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