Mutations in the P. falciparum Digestive Vacuole Transmembrane Protein PfCRT and Evidence for Their Role in Chloroquine Resistance
| Autor: | Amar Bir Singh Sidhu, Bronwen Naudé, Kirk W. Deitsch, Angela K. Talley, Takashi Nomura, Roland A. Cooper, Sergey M. Dzekunov, Lyann M. B. Ursos, David A. Fidock, John C. Wootton, Paul D. Roepe, Thomas E. Wellems, Xin-zhuan Su, Michael T. Ferdig |
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| Rok vydání: | 2000 |
| Předmět: |
Molecular Sequence Data
Plasmodium falciparum Drug Resistance Protozoan Proteins Vacuole Transfection medicine.disease_cause Polymerase Chain Reaction Article Animals Genetically Modified Chloroquine parasitic diseases medicine Animals Humans Amino Acid Sequence Molecular Biology Gene Genetics Mutation biology Membrane transport protein Point mutation Membrane Proteins Membrane Transport Proteins Exons Cell Biology biology.organism_classification Molecular biology Recombinant Proteins Transmembrane protein Tetrahydrofolate Dehydrogenase Verapamil Vacuoles Mutagenesis Site-Directed biology.protein Digestive System medicine.drug |
| Zdroj: | Molecular Cell. 6:861-871 |
| ISSN: | 1097-2765 |
| DOI: | 10.1016/s1097-2765(05)00077-8 |
| Popis: | 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 K76I 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. |
| Databáze: | OpenAIRE |
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