ArticleeLife2020
Chemical and structural investigation of the paroxetine-human serotonin transporter complex.
Article in eLife, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
49 citing papers in PubMed, 90 citations in OpenAlex.
- Structural and functional basis of antinociceptive action of χ-conotoxin AoIA at the noradrenaline transporter.Nature structural & molecular biology · 2026Article
- Optogenetic Regulation of Localization and Function of Serotonin Transporter by Modulating Its Interaction with Soluble Guanylate Cyclase.International journal of molecular sciences · 2026Article
- From In Vitro Genotoxicity Assays to Human Biomarkers: Interpreting DNA Damage Signals in Long-Term SSRI Therapy through a Translational Neurotoxicology Lens.Neurotoxicity research · 2026Review
- Inhibitors of Sodium-Dependent Serotonin Transporter Protein (SERT) as Potential New Nematicides.Chemistry & biodiversity · 2026Article
- Designing Rigid Protein Fiducials to Visualize GPCR Conformational States.bioRxiv : the preprint server for biology · 2026Article
- Modulation of monoaminergic neurotransmission in substance use disorders: a neuropharmacological perspective focusing on plant-derived metabolites.Frontiers in pharmacology · 2026Review
- Regio- and Stereocontrolled-Synthesis of a Heterocycle Fragment Collection Using Palladium Catalyzed C-H Arylation.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- Inhibition of SERT and NMDAR synergistically confers rapid antidepressant effects of ketamine.National science review · 2025Article
- Structural basis of vilazodone dual binding mode to the serotonin transporter.Nature communications · 2025Article
- Structural insights into the substrate uptake and inhibition of the human creatine transporter (hCRT).Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Design, Synthesis, and Evaluation of 1-Benzylpiperidine and 1-Benzoylpiperidine Derivatives as Dual-Target Inhibitors of Acetylcholinesterase and Serotonin Transporter for Alzheimer's Disease.Molecules (Basel, Switzerland) · 2025Article
- Careful Examination of a Novel Azobenzene Paroxetine Derivative and Its Interactions With Biogenic Amine Transporters.Journal of neurochemistry · 2025Article
- Novel psychedelic interventions for post-traumatic stress disorder and their promise for precision medicine.Therapeutic advances in psychopharmacology · 2025Review
- (-)-Syringaresinol Exerts an Antidepressant-like Activity in Mice by Noncompetitive Inhibition of the Serotonin Transporter.Pharmaceuticals (Basel, Switzerland) · 2024Article
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- High-confidence placement of low-occupancy fragments into electron density using the anomalous signal of sulfur and halogen atoms.Acta crystallographica. Section D, Structural biology · 2024Article
- Membrane transporters in drug development and as determinants of precision medicine.Nature reviews. Drug discovery · 2024Review
- Ligand coupling mechanism of the human serotonin transporter differentiates substrates from inhibitors.Nature communications · 2024Article
- Allosteric modulation of serotonin and dopamine transporters: New insights from computations and experiments.Current research in physiology · 2024Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Antidepressants target the serotonin transporter (SERT) by inhibiting serotonin reuptake. Structural and biochemical studies aiming to understand binding of small-molecules to conformationally dynamic transporters like SERT often require thermostabilizing mutations and antibodies to stabilize a specific conformation, leading to questions about relationships of these structures to the bonafide conformation and inhibitor binding poses of wild-type transporter. To address these concerns, we determined the structures of ∆N72/∆C13 and ts2-inactive SERT bound to paroxetine analogues using single-particle cryo-EM and x-ray crystallography, respectively. We synthesized enantiopure analogues of paroxetine containing either bromine or iodine instead of fluorine. We exploited the anomalous scattering of bromine and iodine to define the pose of these inhibitors and investigated inhibitor binding to Asn177 mutants of ts2-active SERT. These studies provide mutually consistent insights into how paroxetine and its analogues bind to the central substrate-binding site of SERT, stabilize the outward-open conformation, and inhibit serotonin transport.
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What OpenQuestion holds
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.