HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE ADVANCED SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tutulan-Cunita, A. C. Articles by Miyakawa, T. Search for Related Content PubMed PubMed Citation Articles by Tutulan-Cunita, A. C. Articles by Miyakawa, T.

Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima 739-8530, Japan

Multidrug resistance ABC transporter Pdr5p of Saccharomyces cerevisiae is particularly important due to its ability to export a wide range of unrelated substrates. To clarify its function, we generated Pdr5p mutants by random mutagenesis and screened for mutants with altered drug specificity in vivo by using 5 drug compounds. Nine point mutations that caused significant changes in drug specificity distributed throughout the length of Pdr5p, namely, in the extracellular, transmembrane or cytoplasmic regions of the transporter. We then investigated their effects upon drug resistance, using 36 chemically related or distinct substrates. From this study, overall geometry of the Pdr5p was suggested to contribute in acquiring the enormous range of drug specificity. Based on their ability to inhibit the growth of the mutant strains, the 36 tested drugs were classified into: drugs to which the mutants responded differently (Group 1), drugs to which all the mutants showed sensitivity (Group 2), and drugs to which all the mutants exhibited resistance (Group 3). The ability of the compounds to be partitioned to the plasma membrane seemed an important factor for recognition by Pdr5p.

^* Correspondence: E-mail: tmiyaka{at}hiroshima-u.ac.jp

This article has been cited by other articles:

				R. D. Cannon, E. Lamping, A. R. Holmes, K. Niimi, P. V. Baret, M. V. Keniya, K. Tanabe, M. Niimi, A. Goffeau, and B. C. Monk Efflux-Mediated Antifungal Drug Resistance Clin. Microbiol. Rev., April 1, 2009; 22(2): 291 - 321. [Abstract] [Full Text] [PDF]

				R. Ernst, P. Kueppers, C. M. Klein, T. Schwarzmueller, K. Kuchler, and L. Schmitt A mutation of the H-loop selectively affects rhodamine transport by the yeast multidrug ABC transporter Pdr5 PNAS, April 1, 2008; 105(13): 5069 - 5074. [Abstract] [Full Text] [PDF]