Plasmodium falciparum P-type ATPase 4 (PfATP4) (PfATP4)

Plasmodium falciparum P-type ATPase 4 (PfATP4) is an essential cation-translocating transporter located on the plasma membrane of the malaria parasite [2, 6]. It functions as a sodium (Na+) efflux pump that maintains a low cytosolic sodium concentration (~10 mM) against the high-sodium environment of the host erythrocyte, a process vital for the parasite's ionic homeostasis and survival [1, 3]. PfATP4 belongs to the P2D subfamily of ATPases (ENA-type), which are absent in mammals, making it a highly selective and attractive target for antimalarial drug development [8, 9]. Inhibition of PfATP4 by various chemical scaffolds, such as spiroindolones (e.g., cipargamin) and dihydroisoquinolones (e.g., SJ733), causes a rapid and lethal accumulation of intracellular sodium, leading to osmotic swelling and parasite death [2, 11]. While PfATP4 inhibitors have shown potent activity in clinical trials, the emergence of resistance-conferring mutations in the pfatp4 gene poses a significant challenge to their long-term therapeutic utility [2, 13, 15].

Other names

P-type cation-translocating ATPase 4P-type ATPase 4ENA-type ATPasePFL0590cPF3D7_1211900

Inhibition of the PfATP4-mediated sodium efflux pump, leading to rapid intracellular sodium accumulation, osmotic imbalance, and parasite lysis [1, 2, 11].