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

PfATP4 is an essential P-type cation-transporting ATPase in Plasmodium falciparum that functions as a sodium efflux pump. It belongs to the type 2D subfamily of P-type ATPases, which are found only in lower eukaryotes (fungi, protozoa, and bryophytes), making it an attractive drug target[3]. PfATP4 maintains a low cytosolic sodium concentration in the parasite by actively extruding sodium, likely coupled with the influx of hydrogen ions (Na+/H+ countertransport)[1]. This process creates an acid load that is countered by a plasma membrane V-type H+-ATPase. PfATP4 has emerged as a target for multiple, chemically diverse antimalarial compounds, including spiroindolones which have shown faster parasite clearance times than artemisinin in clinical trials[3]. Mutations in PfATP4 confer resistance to these antimalarial compounds, highlighting its importance as a drug target[1][2][3]. The protein cycles between four states with significant structural rearrangements of its cytosolic and transmembrane domains[2].

Other names

P. falciparum ATP4Plasmodium falciparum P-type ATPaseNa+/H+-ATPaseSodium efflux pump

Inhibition of PfATP4 disrupts intracellular sodium homeostasis. Blocks Na+ extrusion from the parasite. Disrupts parasite transmission to mosquitoes. Creates an acid load within the parasite.