Plasmodium falciparum calcium-transporting ATPase 6 (PfATP6) (PfATP6)

Plasmodium falciparum calcium-transporting ATPase 6 (PfATP6) is a P-type ATPase and the sole ortholog of the sarco/endoplasmic reticulum calcium ATPase (SERCA) in the malaria parasite [1, 2]. It plays a critical role in maintaining calcium homeostasis by pumping calcium ions from the parasite's cytoplasm into the endoplasmic reticulum, a process essential for parasite survival and development [2, 8]. PfATP6 has gained significant attention as a proposed primary target for artemisinin and its derivatives, which are the cornerstone of modern malaria treatment [3, 10]. While its role as the definitive target of artemisinins has been a subject of scientific debate, recent studies in heterologous expression systems have reinforced its status as a validated drug target [3, 7]. Mutations in the PfATP6 gene, such as S769N and L263E, have been associated with reduced susceptibility to artemisinins in certain field isolates, although clinical resistance is now primarily linked to the K13 protein [2, 12, 17]. Beyond artemisinins, PfATP6 is sensitive to other SERCA inhibitors like cyclopiazonic acid and thapsigargin, making it a focal point for the development of next-generation antimalarials [1, 5]. The enzyme's distinct pharmacological profile compared to human SERCA isoforms offers a window for therapeutic selectivity [1, 11].

Other names

PfSERCAPfATPase6Sarcoplasmic/endoplasmic reticulum calcium-transporting ATPaseCalcium-transporting ATPase 6

Inhibition of the sarco/endoplasmic reticulum calcium ATPase (SERCA) ortholog, leading to the disruption of intracellular calcium homeostasis and subsequent parasite death.