PMID: 9450972Apr 4, 1998Paper

Genetic separation of FK506 susceptibility and drug transport in the yeast Pdr5 ATP-binding cassette multidrug resistance transporter

Molecular Biology of the Cell
R EgnerKarl Kuchler

Abstract

Overexpression of the yeast Pdr5 ATP-binding cassette transporter leads to pleiotropic drug resistance to a variety of structurally unrelated cytotoxic compounds. To identify Pdr5 residues involved in substrate recognition and/or drug transport, we used a combination of random in vitro mutagenesis and phenotypic screening to isolate novel mutant Pdr5 transporters with altered substrate specificity. A plasmid library containing randomly mutagenized PDR5 genes was transformed into appropriate drug-sensitive yeast cells followed by phenotypic selection of Pdr5 mutants. Selected mutant Pdr5 transporters were analyzed with respect to their expression levels, subcellular localization, drug resistance profiles to cycloheximide, rhodamines, antifungal azoles, steroids, and sensitivity to the inhibitor FK506. DNA sequencing of six PDR5 mutant genes identified amino acids important for substrate recognition, drug transport, and specific inhibition of the Pdr5 transporter. Mutations were found in each nucleotide-binding domain, the transmembrane domain 10, and, most surprisingly, even in predicted extracellular hydrophilic loops. At least some point mutations identified appear to influence folding of Pdr5, suggesting that the folded struc...Continue Reading

References

Dec 1, 1977·Proceedings of the National Academy of Sciences of the United States of America·F SangerA R Coulson
Jan 1, 1992·Annual Review of Cell Biology·C F Higgins
May 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·S E DevineP W Melera
Aug 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·P GrosF Talbot
Jan 2, 1992·Nature·M J Gething, J Sambrook
May 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·K UedaI Pastan
Oct 15, 1984·Journal of Molecular Biology·D EisenbergR Wall
Oct 6, 1995·Cell·C L WardR R Kopito
Sep 1, 1993·Trends in Biochemical Sciences·J Kunz, M N Hall
May 9, 1995·Proceedings of the National Academy of Sciences of the United States of America·A KralliK R Yamamoto
Jan 13, 1995·The Journal of Biological Chemistry·T W Loo, D M Clarke
Sep 13, 1994·Proceedings of the National Academy of Sciences of the United States of America·G J ZamanH J Broxterman
Aug 30, 1994·Biochimica Et Biophysica Acta·E Balzi, A Goffeau
Jul 20, 1993·Journal of Molecular Biology·B Rost, C Sander
Jan 26, 1996·The Journal of Biological Chemistry·M MüllerB Sarkadi
Jul 19, 1996·The Journal of Biological Chemistry·A Kralli, K R Yamamoto
Aug 2, 1996·The Journal of Biological Chemistry·C S Hemenway, J Heitman
Jan 1, 1995·Annual Review of Genetics·M M GottesmanI Pastan
Dec 6, 1996·The Journal of Biological Chemistry·M KolaczkowskiA Goffeau

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Citations

May 20, 2009·The Journal of Membrane Biology·Nathan C RockwellJeremy Thorner
Mar 31, 2005·Biochemical and Biophysical Research Communications·Shogo YamamotoKohei Oda
Sep 19, 2003·International Journal of Antimicrobial Agents·Manuela Schuetzer-MuehlbauerKarl Kuchler
Oct 9, 2002·Molecular Microbiology·Thomas EdlindJoseph Nickels
Jun 14, 2002·The Plant Journal : for Cell and Molecular Biology·Sybille van den BrûleCheryl C Smart
Mar 22, 2008·Proceedings of the National Academy of Sciences of the United States of America·Robert ErnstLutz Schmitt
Dec 12, 2002·Molecular Biology of the Cell·Liliana StalevaSeth J Orlow
Feb 16, 2002·The EMBO Journal·M Cristina CruzJoseph Heitman
Aug 22, 2000·Antimicrobial Agents and Chemotherapy·O MarchettiD Sanglard
Nov 19, 2002·Antimicrobial Agents and Chemotherapy·Kasturi MukhopadhyayRajendra Prasad
Apr 24, 2003·Antimicrobial Agents and Chemotherapy·Christian GauthierMartine Raymond
Feb 14, 2013·Biotechnology for Biofuels·Binbin ChenMatthew Wook Chang
Aug 23, 2001·Bioscience, Biotechnology, and Biochemistry·K HiragaK Oda
Jun 6, 2006·Genetics·Abdul-Kader SouidW-C Winston Shen
Jan 13, 2006·FEBS Letters·Helmut Jungwirth, Karl Kuchler
Sep 30, 2014·FEBS Letters·Amornrat Naranuntarat JensenLaran T Jensen
Apr 4, 2009·Journal of Chromatography. a·T F H Bovee, M G Pikkemaat
Feb 24, 2007·Biochemical and Biophysical Research Communications·John GolinLeopold May
Apr 20, 2005·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Andreea Cristina Tutulan-CunitaTokichi Miyakawa
Mar 27, 2003·Molecular Microbiology·Manuela Schuetzer-MuehlbauerKarl Kuchler
Feb 15, 2005·Biochemical and Biophysical Research Communications·Kazumi HiragaKohei Oda
Aug 15, 2006·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·D SanglardJ Bille
Aug 25, 2004·Annals of Tropical Medicine and Parasitology·L R EmersonD F Wirth

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