ArticleJournal of structural biology2011
Toward understanding the mechanism of action of the yeast multidrug resistance transporter Pdr5p: a molecular modeling study.
Article in Journal of structural biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 47 citations in OpenAlex.
- Multidrug Resistance in Mammals and Fungi-From MDR to PDR: A Rocky Road from Atomic Structures to Transport Mechanisms.International journal of molecular sciences · 2021Review
- Nonsynonymous Mutations in Linker-2 of the Pdr5 Multidrug Transporter Identify a New RNA Stability Element.G3 (Bethesda, Md.) · 2020Article
- Evolutionary engineering and molecular characterization of a caffeine-resistant Saccharomyces cerevisiae strain.World journal of microbiology & biotechnology · 2019Article
- An A666G mutation in transmembrane helix 5 of the yeast multidrug transporter Pdr5 increases drug efflux by enhancing cooperativity between transport sites.Molecular microbiology · 2019Article
- Structures of the Multidrug Transporter P-glycoprotein Reveal Asymmetric ATP Binding and the Mechanism of Polyspecificity.The Journal of biological chemistry · 2017Article
- Protein engineering of Saccharomyces cerevisiae transporter Pdr5p identifies key residues that impact Fusarium mycotoxin export and resistance to inhibition.MicrobiologyOpen · 2016Article
- Positive regulation of the Candida albicans multidrug efflux pump Cdr1p function by phosphorylation of its N-terminal extension.The Journal of antimicrobial chemotherapy · 2016Article
- Newly identified motifs in Candida albicans Cdr1 protein nucleotide binding domains are pleiotropic drug resistance subfamily-specific and functionally asymmetric.Scientific reports · 2016Article
- Mutations of charged amino acids at the cytoplasmic end of transmembrane helix 2 affect transport activity of the budding yeast multidrug resistance protein Pdr5p.FEMS yeast research · 2016Article
- Jump into a New Fold-A Homology Based Model for the ABCG2/BCRP Multidrug Transporter.PloS one · 2016Article
- Mutational Analysis of Intracellular Loops Identify Cross Talk with Nucleotide Binding Domains of Yeast ABC Transporter Cdr1p.Scientific reports · 2015Article
- The multidrug transporter Pdr5 on the 25th anniversary of its discovery: an important model for the study of asymmetric ABC transporters.The Biochemical journal · 2015Review
- The ABC of Phytohormone Translocation.Planta medica · 2015Review
- Evidence for a molecular diode-based mechanism in a multispecific ATP-binding cassette (ABC) exporter: SER-1368 as a gatekeeping residue in the yeast multidrug transporter Pdr5.The Journal of biological chemistry · 2014Article
- Generating symmetry in the asymmetric ATP-binding cassette (ABC) transporter Pdr5 from Saccharomyces cerevisiae.The Journal of biological chemistry · 2014Article
- Yeast ABC proteins involved in multidrug resistance.Cellular & molecular biology letters · 2014Review
- The deviant ATP-binding site of the multidrug efflux pump Pdr5 plays an active role in the transport cycle.The Journal of biological chemistry · 2013Article
- Insight into pleiotropic drug resistance ATP-binding cassette pump drug transport through mutagenesis of Cdr1p transmembrane domains.The Journal of biological chemistry · 2013Article
- Transporter engineering for improved tolerance against alkane biofuels in Saccharomyces cerevisiae.Biotechnology for biofuels · 2013Article
- The transmission interface of the Saccharomyces cerevisiae multidrug transporter Pdr5: Val-656 located in intracellular loop 2 plays a major role in drug resistance.Antimicrobial agents and chemotherapy · 2013Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Pleotropic drug resistant protein 5 (Pdr5p) is a plasma membrane ATP-binding cassette (ABC) transporter and the major drug efflux pump in Saccharomyces cerevisiae. The Pdr5p family of fungal transporters possesses a number of structural features significantly different from other modeled or crystallized ABC transporters, which include a reverse topology, an atypical ATP-binding site, a very low sequence similarity in the transmembrane section and long linkers between domains. These features present a considerable hurdle in molecular modeling studies of these important transporters. Here, we report the creation of an atomic model of Pdr5p based on a combination of homology modeling and ab initio methods, incorporating information from consensus transmembrane segment prediction, residue lipophilicity, and sequence entropy. Reported mutations in the transmembrane substrate-binding pocket that altered drug-resistance were used to validate the model, and one mutation that changed the communication pattern between transmembrane and nucleotide-binding domains was used in model improvement. The predictive power of the model was demonstrated experimentally by the increased sensitivity of yeast mutants to clotrimazole having alanine substitutions for Thr1213 and Gln1253, which are predicted to be in the substrate-binding pocket, without reducing the amount of Pdr5p in the plasma membrane. The quality and reliability of our model are discussed in the context of various approaches used for modeling different parts of the structure.
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