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Multidrug efflux pumps: Substrate selection in ATP‐binding cassette multidrug efflux pumps – first come, first served?
Author(s) -
Ernst Robert,
Kueppers Petra,
Stindt Jan,
Kuchler Karl,
Schmitt Lutz
Publication year - 2010
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2009.07485.x
Subject(s) - multiple drug resistance , efflux , atp binding cassette transporter , biology , p glycoprotein , transporter , multidrug resistance associated proteins , drug resistance , biochemistry , microbiology and biotechnology , gene
Multidrug resistance is a major challenge in the therapy of cancer and pathogenic fungal infections. More than three decades ago, P‐glycoprotein was the first identified multidrug transporter. It has been studied extensively at the genetic and biochemical levels ever since. Pdr5, the most abundant ATP‐binding cassette transporter in Saccharomyces cerevisiae , is highly homologous to azole‐resistance‐mediating multidrug transporters in fungal pathogens, and a focus of clinical drug resistance research. Despite functional equivalences, P‐glycoprotein and Pdr5 exhibit striking differences in their architecture and mechanisms. In this minireview, we discuss the mechanisms of substrate selection and multidrug transport by comparing the fraternal twins P‐glycoprotein and Pdr5. We propose that substrate selection in eukaryotic multidrug ATP‐binding cassette transporters is not solely determined by structural features of the transmembrane domains but also by their dynamic behavior.