ArticleThe Journal of biological chemistry2013
Identification of conformationally sensitive residues essential for inhibition of vesicular monoamine transport by the noncompetitive inhibitor tetrabenazine.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 29 citations in OpenAlex.
- SOM3355: a unique pharmacological profile combining VMAT1 inhibition, VMAT2-mediated dopamine modulation, and βFrontiers in pharmacology · 2026Article
- Molecular basis of vesicular monoamine transport and neurological drug interactions.Cell reports · 2025Article
- Neurotransmitter recognition by human vesicular monoamine transporter 2.Nature communications · 2024Article
- Article
- Article
- Packaging monoamine neurotransmitters.Cell research · 2024Article
- Transport and inhibition mechanism for VMAT2-mediated synaptic vesicle loading of monoamines.Cell research · 2024Article
- Article
- Inhibition of VMAT2 by β2-adrenergic agonists, antagonists, and the atypical antipsychotic ziprasidone.Communications biology · 2022Article
- The ins and outs of vesicular monoamine transporters.The Journal of general physiology · 2018Review
- Selective accumulation of biotin in arterial chemoreceptors: requirement for carotid body exocytotic dopamine secretion.The Journal of physiology · 2016Article
- Emulating proton-induced conformational changes in the vesicular monoamine transporter VMAT2 by mutagenesis.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Crystal structures of MdfA complexed with acetylcholine and inhibitor reserpine.Biophysics reports · 2016Article
- Synthesis of (±)-Tetrabenazine by Visible Light Photoredox Catalysis.The Journal of organic chemistry · 2015Article
- Multidrug efflux pumps from Enterobacteriaceae, Vibrio cholerae and Staphylococcus aureus bacterial food pathogens.International journal of environmental research and public health · 2015Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Vesicular monoamine transporter 2 (VMAT2) transports monoamines into storage vesicles in a process that involves exchange of the charged monoamine with two protons. VMAT2 is a member of the DHA12 family of multidrug transporters that belongs to the major facilitator superfamily of secondary transporters. Tetrabenazine (TBZ) is a non-competitive inhibitor of VMAT2 that is used in the treatment of hyperkinetic disorders associated with Huntington disease and Tourette syndrome. Previous biochemical studies suggested that the recognition site for TBZ and monoamines is different. However, the precise mechanism of TBZ interaction with VMAT2 remains unknown. Here we used a random mutagenesis approach and selected TBZ-resistant mutants. The mutations clustered around the lumenal opening of the transporter and mapped to either conserved proline or glycine, or to residues immediately adjacent to conserved proline and glycine. Directed mutagenesis provides further support for the essential role of the latter residues. Our data strongly suggest that the conserved α-helix breaking residues identified in this work play an important role in conformational rearrangements required for TBZ binding and substrate transport. Our results provide a novel insight into the mechanism of transport and TBZ binding by VMAT2.
Indexed as
Identifiers
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.