Reference: Ernst R, et al. (2010) Multidrug efflux pumps: substrate selection in ATP-binding cassette multidrug efflux pumps--first come, first served? FEBS J 277(3):540-9

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Abstract


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.

Reference Type
Journal Article | Research Support, Non-U.S. Gov't | Review
Authors
Ernst R, Kueppers P, Stindt J, Kuchler K, Schmitt L
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