ArticleeLife2024
Structural mechanisms for VMAT2 inhibition by tetrabenazine.
Article in eLife, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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.
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Who cites it
21 citing papers in PubMed, 12 citations in OpenAlex.
- Antidepressant-Like Effects ofPharmaceuticals (Basel, Switzerland) · 2026Article
- Deciphering Ibogaine's Matrix Pharmacology: Multiple Transporter Modulation at Serotonin Synapses.Journal of the American Chemical Society · 2026Article
- Evaluation of the Relationship between Vesicular Monoamine Transporter 2 (VMAT2) Inhibition and Neurologic Adverse Events in Approved Drugs.ACS pharmacology & translational science · 2026Article
- Deutetrabenazine in Hyperkinetic Movement Disorders: VMAT2 Modulation From Choreiform Disorders to Hyperkinetic Dystonic Syndromes.Journal of central nervous system disease · 2026Review
- SOM3355: a unique pharmacological profile combining VMAT1 inhibition, VMAT2-mediated dopamine modulation, and βFrontiers in pharmacology · 2026Article
- Effects of Vitamin C Supplementation on Tetrabenazine Treatment in a Caenorhabditis elegans Huntington's Disease Model.microPublication biology · 2026Article
- Molecular basis of vesicular monoamine transport and neurological drug interactions.Cell reports · 2025Article
- The SLC-ome of membrane transport: From molecular discovery to physiology and clinical applications.Physiological reviews · 2025Review
- AI-Enhanced Transcriptomic Discovery of Druggable Targets and Repurposed Therapies for Huntington's Disease.Brain sciences · 2025Review
- Update on the Symptomatic Treatment of Huntington's Disease: From Pathophysiology to Clinical Practice.International journal of molecular sciences · 2025Review
- Article
- Electroconvulsive therapy for depression and oral dyskinesia in a patient who developed parkinsonism induced by valbenazine.PCN reports : psychiatry and clinical neurosciences · 2025Article
- Structure and mechanism of human vesicular polyamine transporter.Nature communications · 2025Article
- Article
- Real-world safety analysis of deutetrabenazine post-marketing: a disproportionality study leveraging the FDA Adverse Event Reporting System (FAERS) database.BMC pharmacology & toxicology · 2025Article
- Drug inhibition and substrate transport mechanisms of human VMAT2.Nature communications · 2025Article
- ATP-Binding Cassette and Solute Carrier Transporters: Understanding Their Mechanisms and Drug Modulation Through Structural and Modeling Approaches.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Engineering of a mammalian VMAT2 for cryo-EM analysis results in non-canonical protein folding.Nature communications · 2024Article
- VMAT structures reveal exciting targets for drug development.Trends in pharmacological sciences · 2024Review
- Packaging monoamine neurotransmitters.Cell research · 2024Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The vesicular monoamine transporter 2 (VMAT2) is a proton-dependent antiporter responsible for loading monoamine neurotransmitters into synaptic vesicles. Dysregulation of VMAT2 can lead to several neuropsychiatric disorders including Parkinson's disease and schizophrenia. Furthermore, drugs such as amphetamine and MDMA are known to act on VMAT2, exemplifying its role in the mechanisms of actions for drugs of abuse. Despite VMAT2's importance, there remains a critical lack of mechanistic understanding, largely driven by a lack of structural information. Here, we report a 3.1 Å resolution cryo-electron microscopy (cryo-EM) structure of VMAT2 complexed with tetrabenazine (TBZ), a non-competitive inhibitor used in the treatment of Huntington's chorea. We find TBZ interacts with residues in a central binding site, locking VMAT2 in an occluded conformation and providing a mechanistic basis for non-competitive inhibition. We further identify residues critical for cytosolic and lumenal gating, including a cluster of hydrophobic residues which are involved in a lumenal gating strategy. Our structure also highlights three distinct polar networks that may determine VMAT2 conformational dynamics and play a role in proton transduction. The structure elucidates mechanisms of VMAT2 inhibition and transport, providing insights into VMAT2 architecture, function, and the design of small-molecule therapeutics.
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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.