ArticlePloS one2012
A steered molecular dynamics study of binding and translocation processes in the GABA transporter.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- Structural insights into a conserved mechanism of choline translocation through CHT.Science advances · 2026Article
- Molecular Modeling of the Pathogenetic Mechanisms of Neuropsychiatric Disorders.International journal of molecular sciences · 2026Review
- What Determines the Directionality of Kinesins? Studying the Anomalous Directionality of Nonclaret Disjunctional Motor Mutants.Journal of the American Chemical Society · 2026Article
- On the Control of Directionality of Myosin.Journal of the American Chemical Society · 2024Article
- Computational studies on the catalytic potential of the double active site for enzyme engineering.Scientific reports · 2024Article
- A comparative review on the well-studied GAT1 and the understudied BGT-1 in the brain.Frontiers in physiology · 2023Review
- Article
- Structural basis of GABA reuptake inhibition.Nature · 2022Article
- Rational approaches for the design of various GABA modulators and their clinical progression.Molecular diversity · 2021Review
- Molecular Determinants and Pharmacological Analysis for a Class of Competitive Non-transported Bicyclic Inhibitors of the Betaine/GABA Transporter BGT1.Frontiers in chemistry · 2021Article
- Glycine Transporter 2: Mechanism and Allosteric Modulation.Frontiers in molecular biosciences · 2021Review
- Caver Web 1.0: identification of tunnels and channels in proteins and analysis of ligand transport.Nucleic acids research · 2019Article
- Development of Positron Emission Tomography Radiotracers for the GABA Transporter 1.ACS chemical neuroscience · 2018Article
- Structure, Function, and Modulation of γ-Aminobutyric Acid Transporter 1 (GAT1) in Neurological Disorders: A Pharmacoinformatic Prospective.Frontiers in chemistry · 2018Review
- Evidence for a Revised Ion/Substrate Coupling Stoichiometry of GABA Transporters.The Journal of membrane biology · 2015Article
- A binding mode hypothesis of tiagabine confirms liothyronine effect on γ-aminobutyric acid transporter 1 (GAT1).Journal of medicinal chemistry · 2015Article
- Pharmacological identification of a guanidine-containing β-alanine analogue with low micromolar potency and selectivity for the betaine/GABA transporter 1 (BGT1).Neurochemical research · 2014Article
- How drugs get into cells: tested and testable predictions to help discriminate between transporter-mediated uptake and lipoidal bilayer diffusion.Frontiers in pharmacology · 2014Review
- Investigation of the binding network of IGF-I on the cavity surface of IGFBP4.Journal of molecular modeling · 2013Article
- Characterizing changes in the rate of protein-protein dissociation upon interface mutation using hotspot energy and organization.PLoS computational biology · 2013Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The entire substrate translocation pathway in the human GABA transporter (GAT-1) was explored for the endogenous substrate GABA and the anti-convulsive drug tiagabine. Following a steered molecular dynamics (SMD) approach, in which a harmonic restraining potential is applied to the ligand, dissociation and re-association of ligands were simulated revealing events leading to substrate (GABA) translocation and inhibitor (tiagabine) mechanism of action. We succeeded in turning the transporter from the outward facing occluded to the open-to-out conformation, and also to reorient the transporter to the open-to-in conformation. The simulations are validated by literature data and provide a substrate pathway fingerprint in terms of which, how, and in which sequence specific residues are interacted with. They reveal the essential functional roles of specific residues, e.g. the role of charged residues in the extracellular vestibule including two lysines (K76 (TM1) and K448 (TM10)) and a TM6-triad (D281, E283, and D287) in attracting and relocating substrates towards the secondary/interim substrate-binding site (S2). Likewise, E101 is highlighted as essential for the relocation of the substrate from the primary substrate-binding site (S1) towards the cytoplasm.
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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.