title: Purified Plasmodium falciparum multi-drug resistance protein (PfMDR 1) binds a high affinity chloroquine analogue.
abstract: We utilize the recent successful overexpression of recombinant Plasmodium falciparum multi-drug resistance transporter, purification and reconstitution of the protein, and a novel high affinity chloroquine analogue to probe hypothesized interaction between the transporter and quinoline drugs. Results suggest that PfMDR1 binding sites for chloroquine, mefloquine, and quinine overlap, that P. falciparum chloroquine resistance transporter has intrinsically higher affinity for chloroquine relative to P. falciparum multi-drug resistance transporter, and that there is an isoform specific competition between the two transporters for binding of quinoline antimalarial drugs.
authors.affiliation: Department of Chemistry, Georgetown University, 37th and O Streets, Washington, DC 20057, USA.
authors.forename: Perri
authors.initials: P
authors.lastname: Pleeter
authors.forename: Jacqueline K
authors.initials: JK
authors.lastname: Lekostaj
authors.forename: Paul D
authors.initials: PD
authors.lastname: Roepe
mesh_terms: D000962:Antimalarials / Q000378:metabolism* / Q000494:pharmacology; D001665:Binding Sites; D002738:Chloroquine / Q000378:metabolism* / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D015767:Mefloquine / Q000378:metabolism; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000302:isolation & purification / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000187:drug effects / Q000378:metabolism*; D011485:Protein Binding; D011803:Quinine / Q000378:metabolism
chemical_list: D000962:Antimalarials; D002738:Chloroquine; D015767:Mefloquine; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D011803:Quinine; C513498:Mdr1 protein, Plasmodium falciparum