title: A single S1034C mutation confers altered drug sensitivity to PfMDR1 ATPase activity that is characteristic of the 7G8 isoform.
abstract: The mechanism behind how PfMDR1 may contribute to antimalarial drug resistance is unclear. Transfection studies suggest that PfMDR1 mutations may make small contributions to drug sensitivity in a strain-dependent fashion, whereas field data link over expression (not necessarily mutation) of the gene with clinical drug treatment failure. This study dissects the contribution of individual mutations of PfMDR1 that contribute to the unique behavior of the 7G8 PfMDR1 isoform. A single mutation in putative TM 11 (S1034C) is found to abolish drug stimulation of PfMDR1 ATPase activity.
authors.affiliation: Department of Chemistry, Department of Biochemistry, Cellular & Molecular Biology, Lombardi Cancer Center, Georgetown University, 37th and O Streets, Washington, DC 20057, USA.
authors.forename: Jacqueline K
authors.initials: JK
authors.lastname: Lekostaj
authors.forename: Linda E
authors.initials: LE
authors.lastname: Amoah
authors.forename: Paul D
authors.initials: PD
authors.lastname: Roepe
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D019943:Amino Acid Substitution / Q000235:genetics*; D000818:Animals; D004351:Drug Resistance / Q000235:genetics*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics* / Q000378:metabolism; D020125:Mutation, Missense; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism
chemical_list: D000251:Adenosine Triphosphatases; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D020033:Protein Isoforms; C513498:Mdr1 protein, Plasmodium falciparum