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    Nat Struct Mol Biol. 2005 Jul;12(7):628-9. Epub 2005 Jun 5.

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

    Source

    Department of Cellular and Molecular Medicine, Infectious Diseases, St. George's Hospital Medical School, London SW17 0RE, UK.

    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.

    PMID:
    15937493
    [PubMed - indexed for MEDLINE]

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