ArticleNature2016
X-ray structures and mechanism of the human serotonin transporter.
Article in Nature, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 386 papers, 3 of them syntheses that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
386 citing papers in PubMed, 3 syntheses or guidelines pooled it, 688 citations in OpenAlex.
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- Psychopharmacological Therapy Positively Modulates Disease Activity in Inflammatory Bowel Disease: A Systematic Review.International journal of molecular sciences · 2025Pooled it
- Drug-drug interactions between psychiatric medications and MDMA or psilocybin: a systematic review.Psychopharmacology · 2022Pooled it
- Behavioral and Biochemical Effects of Vitexin-Isovitexin-Loaded Microcapsule Combination on Restraint Stress Mouse Model.International journal of molecular sciences · 2026Article
- Structural basis of the transport mechanism of hBGT1.Cell discovery · 2026Article
- Emerging roles of SLC6A14 in digestive system diseases: from amino acid transport to therapeutic targeting.Molecular biology reports · 2026Review
- Identification of novel serotonin transporter (SERT) inhibitors via large-scale machine learning-based virtual screening and molecular dynamics simulations.Molecular diversity · 2026Article
- Neurotropic potential and docking investigations of newly synthesized triazolopyridine and triazolothienopyridine derivatives.RSC advances · 2026Article
- Antimicrobial and Antityrosinase Activity of Bakuchi Oil-Chitosan Hydrogel With In Silico Insights.Chemistry & biodiversity · 2026Article
- Synthesis, neurotropic activity and docking studies of 1,2,4-triazole-linked hybrids based on 2,7-naphthyridine and bispidine rings.RSC advances · 2026Article
- To What Extent Can We Extrapolate Proteochemometric Models: A Case Study for the SLC6 Transporter Family.Molecular informatics · 2026Article
- Structure-guided development of a potent human BCommunications biology · 2026Article
- Cytosolic KJournal of chemical theory and computation · 2026Article
- TRACT assay-based in vitro characterization of substituted cathinones: inhibition and release at the serotonin transporter.Archives of toxicology · 2026Article
- Structural insights into bacterial dimethylsulfoniopropionate import by BCCT-family transporters.The EMBO journal · 2026Article
- Article
- Potential antidepressant properties of aminophylline in male mice exposed to chronic restraint stress.Pharmacological reports : PR · 2026Article
- Optogenetic Regulation of Localization and Function of Serotonin Transporter by Modulating Its Interaction with Soluble Guanylate Cyclase.International journal of molecular sciences · 2026Article
- Beyond neurotransmission: the roles of serotonylation in physiological and pathological processes.Cellular & molecular biology letters · 2026Review
- Stereoselective, sex-dependent 5-HTNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
326 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
The serotonin transporter (SERT) terminates serotonergic signalling through the sodium- and chloride-dependent reuptake of neurotransmitter into presynaptic neurons. SERT is a target for antidepressant and psychostimulant drugs, which block reuptake and prolong neurotransmitter signalling. Here we report X-ray crystallographic structures of human SERT at 3.15 Å resolution bound to the antidepressants (S)-citalopram or paroxetine. Antidepressants lock SERT in an outward-open conformation by lodging in the central binding site, located between transmembrane helices 1, 3, 6, 8 and 10, directly blocking serotonin binding. We further identify the location of an allosteric site in the complex as residing at the periphery of the extracellular vestibule, interposed between extracellular loops 4 and 6 and transmembrane helices 1, 6, 10 and 11. Occupancy of the allosteric site sterically hinders ligand unbinding from the central site, providing an explanation for the action of (S)-citalopram as an allosteric ligand. These structures define the mechanism of antidepressant action in SERT, and provide blueprints for future drug design.
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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.