Plasmodium falciparum chloroquine resistance transporter is a H+-coupled polyspecific nutrient and drug exporter

Proceedings of the National Academy of Sciences of the United States of America
Narinobu JugeYoshinori Moriyama

Abstract

Extrusion of chloroquine (CQ) from digestive vacuoles through the Plasmodium falciparum CQ resistance transporter (PfCRT) is essential to establish CQ resistance of the malaria parasite. However, the physiological relevance of PfCRT and how CQ-resistant PfCRT gains the ability to transport CQ remain unknown. We prepared proteoliposomes containing purified CQ-sensitive and CQ-resistant PfCRTs and measured their transport activities. All PfCRTs tested actively took up tetraethylammonium, verapamil, CQ, basic amino acids, polypeptides, and polyamines at the expense of an electrochemical proton gradient. CQ-resistant PfCRT exhibited decreased affinity for CQ, resulting in increased CQ uptake. Furthermore, CQ competitively inhibited amino acid transport. Thus, PfCRT is a H(+)-coupled polyspecific nutrient and drug exporter.

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Citations

Mar 22, 2016·Tropical Parasitology·Hiasindh Ashmi Antony, Subhash Chandra Parija
Oct 31, 2015·Annual Review of Pharmacology and Toxicology·Hiroshi OmoteYoshinori Moriyama
Jul 3, 2015·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Yoshinori Moriyama
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Aug 5, 2017·The Journal of Biological Chemistry·Naziha BakouhMichael Lanzer
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