ArticleThe EMBO journal2017
Mechanism of formate-nitrite transporters by dielectric shift of substrate acidity.
Article in The EMBO journal, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 64 citations in OpenAlex.
- Phenylalanine Versus Tyrosine (Pos. 367/332 in MCT1/MCT4) in the Substrate Binding Site Defines Affinity and Preferred Directionality of Human Monocarboxylate Transporters 1-4.Acta physiologica (Oxford, England) · 2026Article
- Intrinsic Asymmetry in Weak Acid Transmembrane Transporters.Biomolecules · 2026Review
- Conserved hydrophilic checkpoints tune FocA-mediated formate:HNature communications · 2025Article
- Intracellular formate modulates a motility-invasion switch in Salmonella Typhimurium.PLoS pathogens · 2025Article
- Addressing the Intracellular Vestibule of the Plasmodial Lactate Transporter PfFNT by p-Substituted Inhibitors Amplifies In Vitro Activity.Journal of medicinal chemistry · 2024Article
- TheAntimicrobial agents and chemotherapy · 2023Article
- Human monocarboxylate transporters accept and relay protons via the bound substrate for selectivity and activity at physiological pH.PNAS nexus · 2023Article
- Genomic insight into strategy, interaction and evolution of nitrifiers in metabolizing key labile-dissolved organic nitrogen in different environmental niches.Frontiers in microbiology · 2023Article
- Heterologous expression of formate dehydrogenase enables photoformatotrophy in the emerging model microalga,Frontiers in bioengineering and biotechnology · 2023Article
- OptimizingFrontiers in bioengineering and biotechnology · 2023Article
- Local Attraction of Substrates and Co-Substrates Enhances Weak Acid and Base Transmembrane Transport.Biomolecules · 2022Review
- Distinguishing functional from structural roles of conserved pore residues during formate translocation by the FocA anion channel.MicrobiologyOpen · 2022Article
- Article
- Functional Annotation of Hypothetical Proteins From theBioinformatics and biology insights · 2022Article
- A single amino acid exchange converts FocA into a unidirectional efflux channel for formate.Microbiology (Reading, England) · 2022Article
- Discovery and Development of Inhibitors of the Plasmodial FNT-Type Lactate Transporter as Novel Antimalarials.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Article
- Fluorescence Cross-Correlation Spectroscopy Yields True Affinity and Binding Kinetics ofPharmaceuticals (Basel, Switzerland) · 2021Article
- Pentafluoro-3-hydroxy-pent-2-en-1-ones Potently Inhibit FNT-Type Lactate Transporters from all Five Human-Pathogenic Plasmodium Species.ChemMedChem · 2021Article
- Structural basis of transport and inhibition of the Plasmodium falciparum transporter PfFNT.EMBO reports · 2021Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bacterial formate-nitrite transporters (FNTs) regulate the metabolic flow of small, weak mono-acids. Recently, the eukaryotic PfFNT was identified as the malaria parasite's lactate transporter and novel drug target. Despite crystal data, central mechanisms of FNT gating and transport remained unclear. Here, we show elucidation of the FNT transport mechanism by single-step substrate protonation involving an invariant lysine in the periplasmic vestibule. Opposing earlier gating hypotheses and electrophysiology reports, quantification of total uptake by radiolabeled substrate indicates a permanently open conformation of the bacterial formate transporter, FocA, irrespective of the pH Site-directed mutagenesis, heavy water effects, mathematical modeling, and simulations of solvation imply a general, proton motive force-driven FNT transport mechanism: Electrostatic attraction of the acid anion into a hydrophobic vestibule decreases substrate acidity and facilitates protonation by the bulk solvent. We define substrate neutralization by proton transfer for transport via a hydrophobic transport path as a general theme of the Amt/Mep/Rh ammonium and formate-nitrite transporters.
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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.