title: Potent competitive inhibition of drug binding to the Saccharomyces cerevisiae ABC exporter Pdr5p by the hydrophobic estradiol-derivative RU49953.
abstract: The hydrophobic estradiol-derivative RU49953 inhibits the energy-dependent interaction of yeast multidrug-transporter Pdr5p with its fluorescent drug-substrate rhodamine 6G. The potent inhibition is competitive towards drug binding (Ki=23+/-6 nM), whereas nucleoside-triphosphate hydrolysis is two-orders-of-magnitude less sensitive. RU49953 constitutes the most efficient inhibitor of drug binding to a yeast multidrug ABC exporter reported so far.
authors.affiliation: Institut de Biologie et Chimie des Protéines, UMR 5086 CNRS-Université Claude Bernard Lyon I, IFR 128 BioSciences Lyon-Gerland, 7 Passage du Vercors, 69367 Lyon, France.
authors.forename: Gwenaëlle
authors.initials: G
authors.lastname: Conseil
authors.forename: José M
authors.initials: JM
authors.lastname: Perez-Victoria
authors.forename: J Michel
authors.initials: JM
authors.lastname: Renoir
authors.forename: André
authors.initials: A
authors.lastname: Goffeau
authors.forename: Attilio
authors.initials: A
authors.lastname: Di Pietro
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001667:Binding, Competitive / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005456:Fluorescent Dyes / Q000378:metabolism; D015735:Mifepristone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D012235:Rhodamines / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D018528:ATP-Binding Cassette Transporters; D005456:Fluorescent Dyes; C092438:PDR5 protein, S cerevisiae; C422205:RU49953; D012235:Rhodamines; D029701:Saccharomyces cerevisiae Proteins; C026188:rhodamine 6G; D015735:Mifepristone