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• W2143279537 abstract "The malaria parasite's chloroquine resistance transporter (CRT) is an integral membrane protein localized to the parasite's acidic digestive vacuole. The function of CRT is not known and the protein was originally described as a transporter simply because it possesses 10 transmembrane domains. In wild-type (chloroquine-sensitive) parasites, chloroquine accumulates to high concentrations within the digestive vacuole and it is through interactions in this compartment that it exerts its antimalarial effect. Mutations in CRT can cause a decreased intravacuolar concentration of chloroquine and thereby confer chloroquine resistance. However, the mechanism by which they do so is not understood. In this paper we present the results of a detailed bioinformatic analysis that reveals that CRT is a member of a previously undefined family of proteins, falling within the drug/metabolite transporter superfamily. Comparisons between CRT and other members of the superfamily provide insight into the possible role of the protein and into the significance of the mutations associated with the chloroquine resistance phenotype. The protein is predicted to function as a dimer and to be oriented with its termini in the parasite cytosol. The key chloroquine-resistance-conferring mutation (K76T) is localized in a region of the protein implicated in substrate selectivity. The mutation is predicted to alter the selectivity of the protein such that it is able to transport the cationic (protonated) form of chloroquine down its steep concentration gradient, out of the acidic vacuole, and therefore away from its site of action." @default.
• W2143279537 created "2016-06-24" @default.
• W2143279537 creator A5042625619 @default.
• W2143279537 creator A5054910765 @default.
• W2143279537 date "2004-06-02" @default.
• W2143279537 modified "2023-09-25" @default.
• W2143279537 title "The Malaria Parasite's Chloroquine Resistance Transporter is a Member of the Drug/Metabolite Transporter Superfamily" @default.
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• W2143279537 doi "https://doi.org/10.1093/molbev/msh205" @default.
• W2143279537 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/15240840" @default.
• W2143279537 hasPublicationYear "2004" @default.
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