Mutations in the P. falciparum digestive vacuole transmembrane protein PfCRT and evidence for their role in chloroquine resistance. Academic Article uri icon

Overview

MeSH

  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Digestive System
  • Drug Resistance
  • Exons
  • Humans
  • Membrane Transport Proteins
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Polymerase Chain Reaction
  • Recombinant Proteins
  • Tetrahydrofolate Dehydrogenase
  • Transfection
  • Verapamil

MeSH Major

  • Chloroquine
  • Membrane Proteins
  • Plasmodium falciparum
  • Protozoan Proteins
  • Vacuoles

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.

publication date

  • October 2000

has subject area

  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Chloroquine
  • Digestive System
  • Drug Resistance
  • Exons
  • Humans
  • Membrane Proteins
  • Membrane Transport Proteins
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Plasmodium falciparum
  • Polymerase Chain Reaction
  • Protozoan Proteins
  • Recombinant Proteins
  • Tetrahydrofolate Dehydrogenase
  • Transfection
  • Vacuoles
  • Verapamil

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC2944663

PubMed ID

  • 11090624

Additional Document Info

start page

  • 861

end page

  • 871

volume

  • 6

number

  • 4