Multidrug resistance: can different keys open the same lock?
Multidrug resistance (MDR), resulting from the energy-dependent efflux of structurally unrelated lipophilic compounds, is a major clinical problem. An important question concerns the number and nature of the drug-binding sites in the MDR proteins. A recent report on the high-resolution structure of QacR, a protein that regulates expression of an MDR protein, shows the presence of several independent, but linked binding sites within a single multifaceted drug-binding pocket. This report, for the first time, provides a basis for the specific binding of multiple drugs to a single protein. The significance of these findings and their relevance to the field of drug resistance is discussed.
Kaur
Parjit
P
Department of Biology, Georgia State University, Atlanta, GA 30303, USA. pkaur@gsu.edu
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism; D000818:Animals; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D018432:Drug Resistance, Multiple / Q000502:physiology*; D006801:Humans; D004364:Pharmaceutical Preparations / Q000378:metabolism*
D018435:ATP Binding Cassette Transporter, Subfamily B; D004364:Pharmaceutical Preparations