J. Mol. Micro. Biotechnol. 3: 207-214
The Pleitropic Drug ABC Transporters from Saccharomyces cerevisiae
Bruce Rogers, Anabelle Decottignies, Marcin Kolaczkowski, Elvira Carvajal, Elisabetta Balzi, and André Goffeau
The Saccharomyces cerevisiae genome contains 16 genes encoding full-size ABC transporters. Each
comprises two nucleotide binding folds (NBF) alternating with transmembrane domains (TM). We have studied in
detail three plasma membrane multidrug exporters: Pdr5p (TC3.A.1.205.1) and Snq2p (TC3.A.1.205.2) which
share NBF-TM-NBF-TM topology as well as Yor1p (TC3.A.1.208.3) which exhibits the reciprocal
TM-NBF-TM-NBF topology. The substrate specificity of Pdr5p, Snq2p and Yor1p are largely, but not totally, overlapping as
shown by screening the growth inhibition by 349 toxic compounds of combinatorial deletants of these three
ABC genes. Multiple deletion of 7 ABC genes (YOR1, SNQ2, PDR5, YCF1, PDR10,
PDR11 and PDR15) and of two transcription activation factors
(PDR1 and PDR3) renders the cell from 2 to 200 times more sensitive to
numerous toxic coumpounds including antifungals used in agriculture or medicine. The use of the
pdr1-3 activating mutation and when necessary of the
PDR5 promoter in appropriate multideleted hosts allow high levels of expression
of Pdr5p, Snq2p or Yor1p. These overexpressed proteins exhibit ATPase activity
in vitro and confer considerable multiple drug resistance
in vivo. The latter property can be used for screening specific inhibitors of fungal
and other ABC transporters.
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