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. (C) 2002 Elsevier Science Ltd. All rights reserved.