Calcium-transporting ATPase 1 (PfATP6) (PfATP6)

PfATP6 is a sarcoplasmic/endoplasmic reticulum calcium-transporting ATPase (SERCA) essential for the survival of the malaria parasite Plasmodium falciparum (UniProt Q8I575). It functions as a P-type ATPase that maintains intracellular calcium homeostasis by pumping calcium ions from the cytoplasm into the lumen of the endoplasmic reticulum (PubMed: 12931192). This protein has been identified as a primary putative target for artemisinin and its derivatives (e.g., artesunate, artemether), which are the cornerstone of modern malaria therapy (Nature, 2003, 424:957-961). Artemisinins are thought to inhibit PfATP6 by binding to its transmembrane domain, mimicking the action of the known SERCA inhibitor thapsigargin (Science, 2003). Inhibition of PfATP6 leads to the catastrophic failure of calcium signaling and homeostasis, resulting in parasite death during the erythrocytic stage. Although mutations in the PfKelch13 protein are the current primary markers for artemisinin resistance, specific polymorphisms in PfATP6, such as S769N, have been historically associated with reduced drug sensitivity in certain regions (The Lancet, 2005).

Other names

Sarcoplasmic/endoplasmic reticulum calcium-transporting ATPasePfSERCAPFA0310cPF3D11_0106400P-type ATPase 6

Inhibition of the SERCA-type ATPase pump prevents the sequestration of calcium ions from the cytoplasm into the lumen of the endoplasmic reticulum, resulting in toxic elevation of cytosolic calcium levels and parasite death.