Potent competitive inhibition of drug binding to the Saccharomyces cerevisiae ABC exporter Pdr5p by the hydrophobic estradiol-derivative RU49953.
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.
Conseil
Gwenaëlle
G
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.
Perez-Victoria
José M
JM
Renoir
J Michel
JM
Goffeau
André
A
Di Pietro
Attilio
A
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*
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