Cation-transporting ATPase 4 (PfATP4) (PfATP4)

Cation-transporting ATPase 4 (PfATP4) is an essential P-type ATPase located on the plasma membrane of the malaria parasite Plasmodium falciparum. It functions as a sodium-efflux pump, maintaining a low intracellular sodium concentration against the high sodium environment of the host's blood, which is vital for the parasite's osmotic stability and pH regulation. PfATP4 has emerged as a high-priority therapeutic target because it is inhibited by several chemically diverse classes of next-generation antimalarial compounds, including spiroindolones and aminobenzimidazoles. Inhibition of PfATP4 leads to a rapid and lethal influx of sodium ions into the parasite, resulting in cellular swelling and lysis. Because PfATP4 is structurally distinct from human ion pumps, it offers a high degree of selectivity and remains effective against parasite strains resistant to current frontline treatments like chloroquine and artemisinin.

Other names

PfATP4P-type ATPase 4Sodium-transporting ATPase 4ENA-like ATPasePlasmodium falciparum cation-transporting ATPase 4

Inhibition of PfATP4-mediated sodium efflux, leading to a rapid increase in intracellular sodium concentration, osmotic stress, and parasite death.