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Mutations in the P. falciparum Digestive Vacuole Transmembrane Protein PfCRT and Evidence for Their Role in Chloroquine Resistance
Molecular Cell
  • David A. Fidock, National Institute of Allergy and Infectious Diseases, National Institutes of Health
  • Takashi Nomura, National Institute of Allergy and Infectious Diseases, National Institutes of Health
  • Angela K. Talley, National Institute of Allergy and Infectious Diseases, National Institutes of Health
  • Roland A. Cooper, National Institute of Allergy and Infectious Diseases, National Institutes of Health
  • Sergey M. Dzekunov, Department of Chemistry, Program in Tumor Biology, Lombardi Cancer Center, Georgetown University
  • Michael T. Ferdig, National Institute of Allergy and Infectious Diseases, National Institutes of Health
  • Lyann M. B. Ursos, Department of Chemistry, Program in Tumor Biology, Lombardi Cancer Center, Georgetown University
  • Amar bir Singh Sidhu, Department of Microbiology and Immunology, Albert Einstein College of Medicine
  • Bronwen Naude, National Institute of Allergy and Infectious Diseases, National Institutes of Health
  • Kirk W. Deitsch, National Institute of Allergy and Infectious Diseases, National Institutes of Health
  • Xin-zhuan Su, National Institute of Allergy and Infectious Diseases, National Institutes of Health
  • John C. Wooten, National Institute of Allergy and Infectious Diseases, National Institutes of Health
  • Paul D. Roepe, Department of Chemistry, Program in Tumor Biology, Lombardi Cancer Center, Georgetown University
  • Thomas E. Wellems, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Document Type
Article
Publication Date
10-1-2000
Disciplines
Department
Natural Sciences and Mathematics
Abstract
The determinant of verapamil-reversible chloroquine resistance (CQR) in a Plasmodium falciparum genetic cross maps to a 36 kb segment of chromosome 7. This segment harbors a 13-exon gene, pfcrt, having point mutations that associate completely with CQR in parasite lines from Asia, Africa, and South America. These data, transfection results, and selection of a CQR line harboring a novel K761 mutation point to a central role for the PfCRT protein in CQR. This transmembrane protein localizes to the parasite digestive vacuole (DV), the site of CQ action, where increased compartment acidification associates with PfCRT point mutations. Mutations in PfCRT may result in altered chloroquine flux or reduced drug binding to hematin through an effect on DV pH.
Publisher Statement
Originally published as Fidock, D. A., Nomura, T., Talley, A. K., Cooper, R. A., Dzekunov, S. M., Ferdig, M. T., ... & Wellems, T. E. (2000). Mutations in the P. falciparum digestive vacuole transmembrane protein PfCRT and evidence for their role in chloroquine resistance. Molecular cell, 6(4), 861-871.
Citation Information
David A. Fidock, Takashi Nomura, Angela K. Talley, Roland A. Cooper, et al.. "Mutations in the P. falciparum Digestive Vacuole Transmembrane Protein PfCRT and Evidence for Their Role in Chloroquine Resistance" Molecular Cell Vol. 6 Iss. 4 (2000) p. 861 - 871 ISSN: 1097-4164
Available at: http://works.bepress.com/roland_cooper/34/