A single amino acid residue can determine the sensitivity of SERCAs to artemisinins

  • A Corrigendum to this article was published on 01 February 2012

Abstract

Artemisinins are the most important class of antimalarial drugs. They specifically inhibit PfATP6, a SERCA-type ATPase of Plasmodium falciparum. Here we show that a single amino acid in transmembrane segment 3 of SERCAs can determine susceptibility to artemisinin. An L263E replacement of a malarial by a mammalian residue abolishes inhibition by artemisinins. Introducing residues found in other Plasmodium spp. also modulates artemisinin sensitivity, suggesting that artemisinins interact with the thapsigargin-binding cleft of susceptible SERCAs.

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Figure 1: Inhibitor-binding sites.

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Acknowledgements

This study was supported by the Wellcome Trust (grant 074395). We thank D. Fidock for invaluable discussions.

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Correspondence to Sanjeev Krishna.

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The authors declare no competing financial interests.

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