Potent competitive inhibition of drug binding to the Saccharomyces cerevisiae ABC exporter Pdr5p by the hydrophobic estradiol-derivative RU49953

Biochim Biophys Acta. 2003 Aug 7;1614(2):131-4. doi: 10.1016/s0005-2736(03)00193-7.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / antagonists & inhibitors
  • ATP-Binding Cassette Transporters / metabolism*
  • Binding, Competitive / drug effects
  • Dose-Response Relationship, Drug
  • Fluorescent Dyes / metabolism
  • Mifepristone / analogs & derivatives*
  • Mifepristone / chemistry
  • Mifepristone / pharmacology*
  • Rhodamines / metabolism
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / antagonists & inhibitors
  • Saccharomyces cerevisiae Proteins / metabolism*

Substances

  • ATP-Binding Cassette Transporters
  • Fluorescent Dyes
  • PDR5 protein, S cerevisiae
  • RU49953
  • Rhodamines
  • Saccharomyces cerevisiae Proteins
  • rhodamine 6G
  • Mifepristone