ArticleAntimicrobial agents and chemotherapy2013
The transmission interface of the Saccharomyces cerevisiae multidrug transporter Pdr5: Val-656 located in intracellular loop 2 plays a major role in drug resistance.
Article in Antimicrobial agents and chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- ATP-driven dynamics and itraconazole binding of the drug efflux pump Cdr1 from Candida glabrata.The EMBO journal · 2026Article
- Use of gain-of-function suppressor screening to elucidateFrontiers in microbiology · 2025Article
- Second-site suppressor mutations reveal connection between the drug-binding pocket and nucleotide-binding domain 1 of human P-glycoprotein (ABCB1).Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2023Article
- Fungal Drug Response and Antimicrobial Resistance.Journal of fungi (Basel, Switzerland) · 2023Review
- The Lipoteichoic Acid-Related Proteins YqgS and LafA Contribute to the Resistance of Listeria monocytogenes to Nisin.Microbiology spectrum · 2022Article
- The first intracellular loop is essential for the catalytic cycle of the human ABCG2 multidrug resistance transporter.FEBS letters · 2020Article
- 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
- In vitro NTPase activity of highly purified Pdr5, a major yeast ABC multidrug transporter.Scientific reports · 2019Article
- Robust, pleiotropic drug resistance 5 (Pdr5)-mediated multidrug resistance is vigorously maintained in Saccharomyces cerevisiae cells during glucose and nitrogen limitation.FEMS yeast research · 2018Article
- 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
- 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
- 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
- Efflux pump proteins in antifungal resistance.Frontiers in pharmacology · 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
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8 authors.
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Abstract
Pdr5 is a major ATP-binding cassette (ABC) multidrug transporter regarded as the founding member of a fungal subfamily of clinically significant efflux pumps. When these proteins are overexpressed, they confer broad-spectrum ultraresistance. To better understand the evolution of these proteins under selective pressure, we exposed a Saccharomyces cerevisiae yeast strain already overexpressing Pdr5 to a lethal concentration of cycloheximide. This approach gave mutations that confer greater resistance to a subset of transport substrates. One of these mutations, V656L, is located in intracellular loop 2 (ICL2), a region predicted by structural studies with several other ABC transporters to play a critical role in the transmission interface between the ATP hydrolysis and drug transport domains. We show that this mutation increases drug resistance, possibly by altering the efficiency with which the energy from ATP hydrolysis is used for transport. Val-656 is a conserved residue, and an alanine substitution creates a nearly null phenotype for drug transport as well as reduced ATPase activity. We posit that despite its unusually small size, ICL2 is part of the transmission interface, and that alterations in this pathway can increase or decrease resistance to a broad spectrum of drugs.
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