ArticleNature2010
Neurotransmitter/sodium symporter orthologue LeuT has a single high-affinity substrate site.
Article in Nature, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
What it found
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Who cites it
87 citing papers in PubMed, 126 citations in OpenAlex.
- From extracellular entry to intracellular release: A water-assisted transport cycle for creatine in SLC6A8.Protein science : a publication of the Protein Society · 2026Article
- Revealing the location and dynamics of a concealed binding site in the dopamine transporter.Nature communications · 2025Article
- A comparative review on the well-studied GAT1 and the understudied BGT-1 in the brain.Frontiers in physiology · 2023Review
- Illumination of serotonin transporter mechanism and role of the allosteric site.Science advances · 2021Article
- A solid-supported membrane electrophysiology assay for efficient characterization of ion-coupled transport.The Journal of biological chemistry · 2021Article
- Heteromeric Solute Carriers: Function, Structure, Pathology and Pharmacology.Advances in experimental medicine and biology · 2021Review
- Glycine Transporter 2: Mechanism and Allosteric Modulation.Frontiers in molecular biosciences · 2021Review
- Identification of a New Allosteric Binding Site for Cocaine in Dopamine Transporter.Journal of chemical information and modeling · 2020Article
- The Amino Terminus of LeuT Changes Conformation in an Environment Sensitive Manner.Neurochemical research · 2020Article
- Structure and Gating Dynamics of NaFrontiers in molecular biosciences · 2019Review
- Clickable photoaffinity ligands for the human serotonin transporter based on the selective serotonin reuptake inhibitor (S)-citalopram.Bioorganic & medicinal chemistry letters · 2018Article
- Tamoxifen Directly Interacts with the Dopamine Transporter.The Journal of pharmacology and experimental therapeutics · 2018Article
- Structural elements required for coupling ion and substrate transport in the neurotransmitter transporter homolog LeuT.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- The LeuT-fold neurotransmitter:sodium symporter MhsT has two substrate sites.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Flipped Phenyl Ring Orientations of Dopamine Binding with Human and Drosophila Dopamine Transporters: Remarkable Role of Three Nonconserved Residues.ACS chemical neuroscience · 2018Article
- Substrate-modulated unwinding of transmembrane helices in the NSS transporter LeuT.Science advances · 2018Article
- Latch and trigger role for R445 in DAT transport explains molecular basis of DTDS.Bioorganic & medicinal chemistry letters · 2018Article
- Article
- Alternating access mechanisms of LeuT-fold transporters: trailblazing towards the promised energy landscapes.Current opinion in structural biology · 2017Review
- Conformational dynamics of a neurotransmitter:sodium symporter in a lipid bilayer.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
27 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Neurotransmitter/sodium symporters (NSSs) couple the uptake of neurotransmitter with one or more sodium ions, removing neurotransmitter from the synaptic cleft. NSSs are essential to the function of chemical synapses, are associated with multiple neurological diseases and disorders, and are the targets of therapeutic and illicit drugs. LeuT, a prokaryotic orthologue of the NSS family, is a model transporter for understanding the relationships between molecular mechanism and atomic structure in a broad range of sodium-dependent and sodium-independent secondary transporters. At present there is a controversy over whether there are one or two high-affinity substrate binding sites in LeuT. The first-reported crystal structure of LeuT, together with subsequent functional and structural studies, provided direct evidence for a single, high-affinity, centrally located substrate-binding site, defined as the S1 site. Recent binding, flux and molecular simulation studies, however, have been interpreted in terms of a model where there are two high-affinity binding sites: the central, S1, site and a second, the S2 site, located within the extracellular vestibule. Furthermore, it was proposed that the S1 and S2 sites are allosterically coupled such that occupancy of the S2 site is required for the cytoplasmic release of substrate from the S1 site. Here we address this controversy by performing direct measurement of substrate binding to wild-type LeuT and to S2 site mutants using isothermal titration calorimetry, equilibrium dialysis and scintillation proximity assays. In addition, we perform uptake experiments to determine whether the proposed allosteric coupling between the putative S2 site and the S1 site manifests itself in the kinetics of substrate flux. We conclude that LeuT harbours a single, centrally located, high-affinity substrate-binding site and that transport is well described by a simple, single-substrate kinetic mechanism.
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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.