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.
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June 2011
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Conference Article|
May 20 2011
The choreography of multidrug export
Rupak Doshi;
Rupak Doshi
1Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, U.K.
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Daniel A.P. Gutmann;
Daniel A.P. Gutmann
1Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, U.K.
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Yvonne S.K. Khoo;
Yvonne S.K. Khoo
1Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, U.K.
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Lisa A. Fagg;
Lisa A. Fagg
1Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, U.K.
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Hendrik W. van Veen
Hendrik W. van Veen
1
1Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, U.K.
1To whom correspondence should be addressed (email hwv20@cam.ac.uk).
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Publisher: Portland Press Ltd
Received:
March 11 2011
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2011 Biochemical Society
2011
Biochem Soc Trans (2011) 39 (3): 807–811.
Article history
Received:
March 11 2011
Citation
Rupak Doshi, Daniel A.P. Gutmann, Yvonne S.K. Khoo, Lisa A. Fagg, Hendrik W. van Veen; The choreography of multidrug export. Biochem Soc Trans 1 June 2011; 39 (3): 807–811. doi: https://doi.org/10.1042/BST0390807
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