ArticlePloS one2018
Thermostabilization and purification of the human dopamine transporter (hDAT) in an inhibitor and allosteric ligand bound conformation.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- (N)-Methanocarba-adenosines as monoamine transporter allosteric inhibitors: Extended NEuropean journal of medicinal chemistry · 2026Article
- Structural basis for pharmacotherapeutic action of triple reuptake inhibitors.Nature communications · 2025Article
- Article
- The Bright Side of Psychedelics: Latest Advances and Challenges in Neuropharmacology.International journal of molecular sciences · 2023Review
- Overview of the structure and function of the dopamine transporter and its protein interactions.Frontiers in physiology · 2023Review
- Article
- Allosteric Modulator KM822 Attenuates Behavioral Actions of Amphetamine inMolecular pharmacology · 2022Article
- Elucidating the Mechanism Behind Sodium-Coupled Neurotransmitter Transporters by Reconstitution.Neurochemical research · 2022Review
- Expanding the repertoire of methanocarba nucleosides from purinergic signaling to diverse targets.RSC medicinal chemistry · 2021Review
- The antidepressant drug vilazodone is an allosteric inhibitor of the serotonin transporter.Nature communications · 2021Article
- Assessment of Paroxetine Molecular Interactions with Selected Monoamine and γ-Aminobutyric Acid Transporters.International journal of molecular sciences · 2021Article
- Hybrid Nanoparticle Platform for Nanoscale Scintillation Proximity Assay.ACS applied nano materials · 2019Article
- Regulatory Aspects of the Vacuolar CAT2 Arginine Transporter ofInternational journal of molecular sciences · 2019Article
- Insights into the mechanism and pharmacology of neurotransmitter sodium symporters.Current opinion in structural biology · 2019Review
- Structure and Gating Dynamics of NaFrontiers in molecular biosciences · 2019Review
- Direct coupling of oligomerization and oligomerization-driven endocytosis of the dopamine transporter to its conformational mechanics and activity.The Journal of biological chemistryArticle
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
The human dopamine transporter (hDAT) plays a major role in dopamine homeostasis and regulation of neurotransmission by clearing dopamine from the extracellular space using secondary active transport. Dopamine is an essential monoamine chemical messenger that regulates reward seeking behavior, motor control, hormonal release, and emotional response in humans. Psychostimulants such as cocaine primarily target the central binding site of hDAT and lock the transporter in an outward-facing conformation, thereby inhibiting dopamine reuptake. The inhibition of dopamine reuptake leads to accumulation of dopamine in the synapse causing heightened signaling. In addition, hDAT is implicated in various neurological disorders and disease-associated neurodegeneration. Despite its significance, the structural studies of hDAT have proven difficult. Instability of hDAT in detergent micelles has been a limiting factor in its successful biochemical, biophysical, and structural characterization. To overcome this hurdle, we identified ligands that stabilize hDAT in detergent micelles. We then screened ~200 single residue mutants of hDAT using a high-throughput scintillation proximity assay and identified a thermostable variant (I248Y). Here we report a robust strategy to overexpress and successfully purify a thermostable variant of hDAT in an inhibitor and allosteric ligand bound conformation.
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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.