Anticancer Drugs, Ionophoric Peptides, and Steroids as Substrates of the Yeast Multidrug Transporter Pdr5p*
@article{Koaczkowski1996AnticancerDI, title={Anticancer Drugs, Ionophoric Peptides, and Steroids as Substrates of the Yeast Multidrug Transporter Pdr5p*}, author={Marcin Kołaczkowski and van der Rest Michel and Anna Cybularz-Kolaczkowska and J. P. Soumillion and Wilhelmus Nicolaas Konings and Goffeau Andr{\'e}}, journal={The Journal of Biological Chemistry}, year={1996}, volume={271}, pages={31543 - 31548} }
Pdr5p is the yeast Saccharomyces cerevisiae ATP-binding cassette transporter conferring resistance to several unrelated drugs. Its high overproduction in Pdr1p transcription factor mutants allows us to study the molecular mechanism of multidrug transport and substrate specificity. We have developed new in vivo and in vitro assays of Pdr5p-mediated drug transport. We show that in spite of little sequence homology, and inverted topology in respect to that of mammalian P-glycoproteins, Pdr5p…
299 Citations
A new function of isonitrile as an inhibitor of the Pdr5p multidrug ABC transporter in Saccharomyces cerevisiae.
- Biology, ChemistryBiochemical and biophysical research communications
- 2005
Enniatin has a new function as an inhibitor of Pdr5p, one of the ABC transporters in Saccharomyces cerevisiae.
- Biology, ChemistryBiochemical and biophysical research communications
- 2005
Chemosensitization of Fluconazole Resistance in Saccharomyces cerevisiae and Pathogenic Fungi by a d-Octapeptide Derivative
- Biology, ChemistryAntimicrobial Agents and Chemotherapy
- 2004
Library deconvolution identified the 4-methoxy-2,3,6-trimethylbenzensulfonyl-substituted d-octapeptide KN20 as a potent Pdr5p ATPase inhibitor which chemosensitized AD/PDR5+ to FLC, itraconazole, and ketoconazole.
Alkylrhodamines enhance the toxicity of clotrimazole and benzalkonium chloride by interfering with yeast pleiotropic ABC-transporters.
- Biology, ChemistryFEMS yeast research
- 2016
Alkylated rhodamines were shown to be non-toxic on mice, which makes them potential components of pharmacological antifungal compositions, and inactivation of Pdr5p had the strongest effect on the accumulation of octylrhodamine inside the cells, which is consistent with the fact that clotrimazole is a substrate of PDR5p.
Alcohols are inhibitors of Saccharomyces cerevisiae multidrug-resistance pumps Pdr5p and Snq2p.
- Medicine, BiologyFEMS yeast research
- 2013
Using a fluorescence diS-C3 diagnostic assay for multidrug-resistance pump inhibitors in a set of isogenic yeast Pdr5p and Snq2p mutants, it is found that n-alcohols variously affect the activity of both pumps, supporting a notion that the inhibitory action may entail a direct interaction of the alcohols with the pump proteins.
Inhibitory effects of gallic acid ester derivatives on Saccharomyces cerevisiae multidrug resistance protein Pdr5p.
- Biology, ChemistryFEMS yeast research
- 2010
The effects of gallic acid derivatives with substitutions either on the ester moiety or in the benzene ring on the activity of Pdr5p are reported, suggesting that these compounds may be a new class of PDR5p inhibitors.
Modulation by flavonoids of cell multidrug resistance mediated by P-glycoprotein and related ABC transporters
- BiologyCellular and Molecular Life Sciences CMLS
- 2002
This review shows that due to similarities in function and maybe in three-dimensional organization of the different transporters, common potential modulators have been found and constitute promising potentialmodulators of multidrug resistance.
Studies with Novel Pdr5p Substrates Demonstrate a Strong Size Dependence for Xenobiotic Efflux*
- BiologyThe Journal of Biological Chemistry
- 2003
It is demonstrated that the Pdr5p transporter is capable of mediating transport of substrates that neither ionize nor have electron pair donors and that are much simpler in structure than those transported by the human MDR1-encoded P-glycoprotein.
Drug transport by reconstituted P-glycoprotein in proteoliposomes. Effect of substrates and modulators, and dependence on bilayer phase state.
- Biology, ChemistryEuropean journal of biochemistry
- 2001
Monitoring of transport in proteoliposomes containing reconstituted Pgp showed a highly unusual biphasic temperature dependence, which suggests that the rate of drug transport by Pgp may be dominated by partitioning of drug into the bilayer.
A mutation of the H-loop selectively affects rhodamine transport by the yeast multidrug ABC transporter Pdr5
- Biology, ChemistryProceedings of the National Academy of Sciences
- 2008
In vivo and in vitro experiments to address the functional asymmetry of NBDs provide important insights into the molecular mechanism of Pdr5 and suggest that not solely the transmembrane domains dictate substrate selection.
References
SHOWING 1-10 OF 35 REFERENCES
Solubilization and characterization of the overexpressed PDR5 multidrug resistance nucleotide triphosphatase of yeast.
- Biology, ChemistryThe Journal of biological chemistry
- 1994
PDR5, a novel yeast multidrug resistance conferring transporter controlled by the transcription regulator PDR1.
- BiologyThe Journal of biological chemistry
- 1994
ATP-dependent transport of vinblastine in vesicles from human multidrug-resistant cells.
- BiologyProceedings of the National Academy of Sciences of the United States of America
- 1988
It is confirmed that multidrug-resistant cells express an energy-dependent plasma membrane transporter for hydrophobic drugs, and a system for the detailed biochemical analysis of this transport process is established.
Identification and Characterization of SNQ2, a New Multidrug ATP Binding Cassette Transporter of the Yeast Plasma Membrane (*)
- Biology, ChemistryThe Journal of Biological Chemistry
- 1995
Disruption of both PDR5 and SNQ2 in a pdr1 mutant decreases the cell growth rate and reveals the presence of at least two other ATP binding cassette proteins in the 160-kDa overexpressed band that have been identified by amino-terminal microsequencing.
Phosphatidylcholine translocase: A physiological role for the mdr2 gene
- Biology, ChemistryCell
- 1994
Azidopine noncompetitively interacts with vinblastine and cyclosporin A binding to P-glycoprotein in multidrug resistant cells.
- Biology, ChemistryThe Journal of biological chemistry
- 1991
Characterization of the adenosine triphosphatase activity of Chinese hamster P-glycoprotein.
- Biology, ChemistryThe Journal of biological chemistry
- 1993
Yeast multidrug resistance: The PDR network
- BiologyJournal of bioenergetics and biomembranes
- 1995
A network of genes involved in multiple drug resistance of the yeastS.
Multidrug resistance in Lactococcus lactis: evidence for ATP‐dependent drug extrusion from the inner leaflet of the cytoplasmic membrane.
- BiologyThe EMBO journal
- 1996
Results demonstrate that the lactococcal MDR transporter functions as a ‘hydrophobic vacuum cleaner’, expelling drugs from the inner leaflet of the lipid bilayer, thereby demonstrating the ability of amphiphilic substrates to partition in the inner Leaflets of the membrane is a prerequisite for recognition by multidrug transporters.