ArticleProceedings of the National Academy of Sciences of the United States of America2012
Transforming a drug/H+ antiporter into a polyamine importer by a single mutation.
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 26 papers.
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Who cites it
26 citing papers in PubMed, 41 citations in OpenAlex.
- Protonated Structure of EmrE Reveals C-terminal Tail Gating Mechanism.bioRxiv : the preprint server for biology · 2026Article
- Understanding, inhibiting, and engineering membrane transporters with high-throughput mutational screens.Cell chemical biology · 2025Review
- Dynamics underlie the drug recognition mechanism by the efflux transporter EmrE.Nature communications · 2024Article
- Functional promiscuity of small multidrug resistance transporters from Staphylococcus aureus, Pseudomonas aeruginosa, and Francisella tularensis.Molecular microbiology · 2024Article
- Activating alternative transport modes in a multidrug resistance efflux pump to confer chemical susceptibility.Nature communications · 2022Article
- High-pH structure of EmrE reveals the mechanism of proton-coupled substrate transport.Nature communications · 2022Article
- Characterization of Proteobacterial Plasmid Integron-EncodedAntimicrobial agents and chemotherapy · 2021Article
- Structural Insights into Transporter-Mediated Drug Resistance in Infectious Diseases.Journal of molecular biology · 2021Review
- Toward a Multipathway Perspective: pH-Dependent Kinetic Selection of Competing Pathways and the Role of the Internal Glutamate in ClThe journal of physical chemistry. B · 2021Article
- Structure and dynamics of the drug-bound bacterial transporter EmrE in lipid bilayers.Nature communications · 2021Article
- Biologia futura: the role of polyamine in plant science.Biologia futura · 2020Review
- Acidification of Cytoplasm in Escherichia coli Provides a Strategy to Cope with Stress and Facilitates Development of Antibiotic Resistance.Scientific reports · 2020Article
- Highly coupled transport can be achieved in free-exchange transport models.The Journal of general physiology · 2020Article
- Inducing conformational preference of the membrane protein transporter EmrE through conservative mutations.eLife · 2019Article
- Identification of an Alternating-Access Dynamics Mutant of EmrE with Impaired Transport.Journal of molecular biology · 2019Article
- The C terminus of the bacterial multidrug transporter EmrE couples drug binding to proton release.The Journal of biological chemistry · 2018Article
- Electrostatic lock in the transport cycle of the multidrug resistance transporter EmrE.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Few Conserved Amino Acids in the Small Multidrug Resistance Transporter EmrE Influence Drug Polyselectivity.Antimicrobial agents and chemotherapy · 2018Article
- Biocide Selective TolC-Independent Efflux Pumps in Enterobacteriaceae.The Journal of membrane biology · 2018Article
- New free-exchange model of EmrE transport.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
EmrE, a multidrug antiporter from Escherichia coli, has presented biochemists with unusual surprises. Here we describe the transformation of EmrE, a drug/H(+) antiporter to a polyamine importer by a single mutation. Antibiotic resistance in microorganisms may arise by mutations at certain chromosomal loci. To investigate this phenomenon, we used directed evolution of EmrE to assess the rate of development of novel specificities in existing multidrug transporters. Strikingly, when a library of random mutants of EmrE was screened for resistance to two major antibacterial drugs--norfloxacin, a fluoroquinolone, and erythromycin, a macrolide--proteins with single mutations were found capable of conferring resistance. The mutation conferring erythromycin resistance resulted from substitution of a fully conserved and essential tryptophan residue to glycine, and, as expected, this protein lost its ability to recognize and transport the classical EmrE substrates. However, this protein functions now as an electrochemical potential driven importer of a new set of substrates: aliphatic polyamines. This mutant provides a unique paradigm to understand the function and evolution of distinct modes of transport.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.