ArticleProceedings of the National Academy of Sciences of the United States of America2012
Manipulating the drug/proton antiport stoichiometry of the secondary multidrug transporter MdfA.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 46 citations in OpenAlex.
- Energetic and structural control of polyspecificity in a multidrug transporter.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Molecular determinants of substrate specificity in the efflux pump CraA fromMicrobiology spectrum · 2025Article
- Structure and mechanism of human vesicular polyamine transporter.Nature communications · 2025Article
- A major facilitator superfamily transporter MdtH inApplied and environmental microbiology · 2024Article
- Review
- Cryo-EM structure of antibacterial efflux transporter QacA from Staphylococcus aureus reveals a novel extracellular loop with allosteric role.The EMBO journal · 2023Article
- Deep mutational scan of a drug efflux pump reveals its structure-function landscape.Nature chemical biology · 2023Article
- Mutagenesis and functional analysis of SotB: A multidrug transporter of the major facilitator superfamily fromFrontiers in microbiology · 2022Article
- Structures and General Transport Mechanisms by the Major Facilitator Superfamily (MFS).Chemical reviews · 2021Article
- Structure and mechanism of a redesigned multidrug transporter from the Major Facilitator Superfamily.Scientific reports · 2020Article
- Recent advances of pH homeostasis mechanisms in Corynebacterium glutamicum.World journal of microbiology & biotechnology · 2019Review
- Dissection of Protonation Sites for Antibacterial Recognition and Transport in QacA, a Multi-Drug Efflux Transporter.Journal of molecular biology · 2019Article
- Structure of an engineered multidrug transporter MdfA reveals the molecular basis for substrate recognition.Communications biology · 2019Article
- Thermodynamic secrets of multidrug resistance: A new take on transport mechanisms of secondary active antiporters.Protein science : a publication of the Protein Society · 2018Review
- Relocation of active site carboxylates in major facilitator superfamily multidrug transporter LmrP reveals plasticity in proton interactions.Scientific reports · 2016Article
- Expanding the Limits of Thermoacidophily in the Archaeon Sulfolobus solfataricus by Adaptive Evolution.Applied and environmental microbiology · 2016Article
- Substrate-bound structure of the E. coli multidrug resistance transporter MdfA.Cell research · 2015Article
- Identification of molecular hinge points mediating alternating access in the vesicular monoamine transporter VMAT2.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Structural comparison of bacterial multidrug efflux pumps of the major facilitator superfamily.Trends in cell & molecular biologyArticle
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multidrug transporters are integral membrane proteins that use cellular energy to actively extrude antibiotics and other toxic compounds from cells. The multidrug/proton antiporter MdfA from Escherichia coli exchanges monovalent cationic substrates for protons with a stoichiometry of 1, meaning that it translocates only one proton per antiport cycle. This may explain why transport of divalent cationic drugs by MdfA is energetically unfavorable. Remarkably, however, we show that MdfA can be easily converted into a divalent cationic drug/≥ 2 proton-antiporter, either by random mutagenesis or by rational design. The results suggest that exchange of divalent cationi c drugs with two (or more) protons requires an additional acidic residue in the multidrug recognition pocket of MdfA. This outcome further illustrates the exceptional promiscuous capabilities of multidrug transporters.
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