Plasmodium falciparum P-type ATPase 4 (PfATP4)

Plasmodium falciparum P-type ATPase 4 (PfATP4) is a cation-transporting enzyme located on the plasma membrane of the malaria parasite during its intraerythrocytic stage (UniProt Q8I0V0). It functions as a sodium-efflux pump, maintaining low intracellular sodium levels against the high-sodium environment of the host red blood cell (Spillman et al., 2013, PubMed: 23934150). This activity is critical for maintaining osmotic balance and regulating the parasite's internal pH. PfATP4 is a validated therapeutic target for several novel classes of antimalarial drugs, most notably the spiroindolones and dihydroisoquinolones (Rottmann et al., 2010, PubMed: 20813920). Inhibition of PfATP4 leads to a rapid influx of sodium ions, resulting in parasite swelling and death via osmotic lysis (Jiménez-Díaz et al., 2014, PubMed: 25248143). Despite its potency as a target, PfATP4 is susceptible to various point mutations that can lead to drug resistance, necessitating ongoing surveillance in clinical settings. Because PfATP4 is distinct from human P-type ATPases, it provides a favorable therapeutic window for drug development.

Other names

P-type Na+-ATPaseSodium-exporting P-type ATPaseCation-transporting ATPase PfATP4PfATP4 protein

Inhibition of the PfATP4 pump prevents the efflux of sodium ions, leading to a rapid increase in intracellular sodium concentration, osmotic swelling, and subsequent parasite lysis (Spillman et al., 2013, PubMed: 23934150).