PfATP6, also known as PfSERCA or PfATPase6, is a calcium ATPase gene encoded by the malaria parasite Plasmodium falciparum. The protein is thought to be a P-type ATPase involved in calcium ion transport.
Resistance to artemisinin antimalarials
It was suggested in 2003 that PfATP6 is a target of artemisinin antimalarials, and also that a single amino acid mutation in the enzyme can mediate resistance to this important group of compounds. The main evidence came from a Xenopus oocyte system describing specific interactions between artemisinins and PfATP6 as well as E255L-mutated mammalian SERCA. However an independent reappraisal in the same system showed that while PfATP6 protein could be detected, it was inactive. In the independent oocyte work, mammalian SERCA and its E255L-mutated version were active but both were insensitive to artemisinin, again in contrast to the original claims. The authors suggested that the original results might have been affected by low ATPase signals, few experimental repeats and large standard deviations. The lack of artemisinin inhibition of E255L mammalian SERCA matched results from heterologous expression in mammalian and yeast cells.
PfATP6 mutations clearly play no role in the reduced artemisinin susceptibility observed in southeast Asia. The consensus is that PfATP6 is not directly involved in artemisinin action or resistance.
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