title: The choreography of multidrug export.
abstract: Multidrug transporters have a crucial role in causing the drug resistance that can arise in infectious micro-organisms and tumours. These integral membrane proteins mediate the export of a broad range of unrelated compounds from cells, including antibiotics and anticancer agents, thus reducing the concentration of these compounds to subtoxic levels in target cells. In spite of intensive research, it is not clear exactly how multidrug transporters work. The present review focuses on recent advancements in the biochemistry and structural biology of bacterial and human multidrug ABC (ATP-binding cassette) transporters. These advancements point to a common mechanism in which polyspecific drug-binding surfaces in the membrane domains are alternately exposed to the inside and outside surface of the membrane in response to the ATP-driven dimerization of nucleotide-binding domains and their dissociation following ATP hydrolysis.
authors: Department of Pharmacology, University of Cambridge, U.K.
authors: Rupak
authors: R
authors: Doshi
authors: Daniel A P
authors: DA
authors: Gutmann
authors: Yvonne S K
authors: YS
authors: Khoo
authors: Lisa A
authors: LA
authors: Fagg
authors: Hendrik W
authors: HW
authors: van Veen