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XB-ART-40264
Science 2009 Sep 25;3255948:1680-2. doi: 10.1126/science.1175667.
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Chloroquine transport via the malaria parasite's chloroquine resistance transporter.

Martin RE, Marchetti RV, Cowan AI, Howitt SM, Bröer S, Kirk K.


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The emergence and spread of chloroquine-resistant Plasmodium falciparum malaria parasites has been a disaster for world health. Resistance is conferred by mutations in the Chloroquine Resistance Transporter (PfCRT), an integral membrane protein localized to the parasite's internal digestive vacuole. These mutations result in a marked reduction in the accumulation of chloroquine (CQ) by the parasite. However, the mechanism by which this occurs is unclear. We expressed both wild-type and resistant forms of PfCRT at the surface of Xenopus laevis oocytes. The resistant form of PfCRT transported CQ, whereas the wild-type protein did not. CQ transport via the mutant PfCRT was inhibited by CQ analogs and by the resistance-reverser verapamil. Thus, CQ resistance is due to direct transport of the drug via mutant PfCRT.

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