Plasmodium falciparum calcium-transporting ATPase 6 (PfATP6)

Plasmodium falciparum calcium-transporting ATPase 6 (PfATP6) is a SERCA-type (sarco/endoplasmic reticulum calcium ATPase) P-type ATPase enzyme found in the malaria parasite P. falciparum. It functions to transport calcium ions from the cytosol into the endoplasmic reticulum, playing a critical role in calcium homeostasis essential for parasite survival[1][2][3][4]. PfATP6 has structural and functional similarity to mammalian SERCAs but differs enough to be specifically targeted by antimalarial drugs. Artemisinin and its derivatives are proposed to inhibit PfATP6 through both allosteric modulation and covalent modification, causing lethal dysregulation of calcium in the parasite[1][2][4]. Mutations in PfATP6 can result in reduced sensitivity to artemisinins, contributing to drug resistance, but resistance mechanisms are complex and involve other factors beyond PfATP6 mutations[2][3][5]. PfATP6 remains an important molecular target for antimalarial therapy and drug development.

Other names

SERCA-type Ca²⁺-ATPaseSarco/endoplasmic reticulum calcium ATPase of PlasmodiumPfSERCA

Inhibition of Ca²⁺ transport by allosteric or covalent binding to ATPase domains, leading to disruption of calcium homeostasis and parasite death[1][2][3][4].\nFor artemisinin, possible covalent binding following activation by heme or iron, leading to enzyme inhibition[1][4][5].