ArticleNature structural & molecular biology2009
Antidepressant specificity of serotonin transporter suggested by three LeuT-SSRI structures.
Article in Nature structural & molecular biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 134 papers, 1 of them a synthesis that pooled it.
What it found
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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
134 citing papers in PubMed, 1 synthesis or guideline pooled it, 239 citations in OpenAlex.
- The serotonin theory of depression: a systematic umbrella review of the evidence.Molecular psychiatry · 2023Pooled it
- Dopamine Transporter and Reward Anticipation in a Dimensional Perspective: A Multimodal Brain Imaging Study.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018Trial
- Pharmacometabolomic mapping of early biochemical changes induced by sertraline and placebo.Translational psychiatry · 2013Trial
- Cross-Species Triage of SERT-Oriented Polyheteroaryl Candidates Prioritizes AD20/UtIA-0108 as an Early Neuroactive Candidate.Current issues in molecular biology · 2026Article
- Perinatal citalopram exposure alters the gut composition and microbial metabolic profiles of Sprague-Dawley rat dams and female offspring but not male offspring.Biology of sex differences · 2025Article
- Systematic metaproteomics mapping reveals functional and ecological landscapes of Ex vivo human gut microbiota responses to therapeutic drugs.Nature communications · 2025Article
- Effects of selective serotonin reuptake inhibitors on the placenta†.Biology of reproduction · 2025Review
- Serotonin 2A receptor attenuates psoriatic inflammation by suppressing IL-23 secretion in monocyte-derived Langerhans cells.Nature communications · 2025Article
- Fluvoxamine: First comprehensive insights into its molecular characteristics and inclusion complexation with β-cyclodextrin.Journal of pharmaceutical analysis · 2025Article
- Psilocybin in pharmacotherapy of obsessive-compulsive disorder.Pharmacological reports : PR · 2024Review
- Uncovering the Elusive Structures and Mechanisms of Prevalent Antidepressants.Advanced therapeutics · 2024Article
- Cryo-EM structure of the dopamine transporter with a novel atypical non-competitive inhibitor bound to the orthosteric site.Journal of neurochemistry · 2024Article
- Taurine and Creatine Transporters as Potential Drug Targets in Cancer Therapy.International journal of molecular sciences · 2023Review
- Inclusion Scenarios and Conformational Flexibility of the SSRI Paroxetine as Perceived from Polymorphism of β-Cyclodextrin-Paroxetine Complex.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Novel Molecular Targets of Antidepressants.Molecules (Basel, Switzerland) · 2022Review
- Truly-Biocompatible Gold Catalysis Enables Vivo-Orthogonal Intra-CNS Release of Anxiolytics.Angewandte Chemie (International ed. in English) · 2022Article
- Truly-Biocompatible Gold Catalysis Enables Vivo-Orthogonal Intra-CNS Release of Anxiolytics.Angewandte Chemie (Weinheim an der Bergstrasse, Germany) · 2022Article
- Advancing insights on β-cyclodextrin inclusion complexes with SSRIs through lens of X-ray diffraction and DFT calculation.International journal of pharmaceutics · 2021Article
- Effects of the Selective Serotonin Reuptake Inhibitor Fluoxetine on Developing Neural Circuits in a Model of the Human Fetal Cortex.International journal of molecular sciences · 2021Article
- Interactions between maternal fluoxetine exposure, the maternal gut microbiome and fetal neurodevelopment in mice.Behavioural brain research · 2021Article
74 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Sertraline and fluoxetine are selective serotonin re-uptake inhibitors (SSRIs) that are widely prescribed to treat depression. They exert their effects by inhibiting the presynaptic plasma membrane serotonin transporter (SERT). All SSRIs possess halogen atoms at specific positions, which are key determinants for the drugs' specificity for SERT. For the SERT protein, however, the structural basis of its specificity for SSRIs is poorly understood. Here we report the crystal structures of LeuT, a bacterial SERT homolog, in complex with sertraline, R-fluoxetine or S-fluoxetine. The SSRI halogens all bind to exactly the same pocket within LeuT. Mutation at this halogen-binding pocket (HBP) in SERT markedly reduces the transporter's affinity for SSRIs but not for tricyclic antidepressants. Conversely, when the only nonconserved HBP residue in both norepinephrine and dopamine transporters is mutated into that found in SERT, their affinities for all the three SSRIs increase uniformly. Thus, the specificity of SERT for SSRIs is dependent largely on interaction of the drug halogens with the protein's HBP.
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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.