ArticleScientific reports2015
Binding site residues control inhibitor selectivity in the human norepinephrine transporter but not in the human dopamine transporter.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 38 citations in OpenAlex.
- (N)-Methanocarba-adenosines as monoamine transporter allosteric inhibitors: Extended NEuropean journal of medicinal chemistry · 2026Article
- Mutational effects of the asparagine198 and glutamate223 residues on the human norepinephrine transporter on basal and HIV-1 Tat protein-induced inhibition of dopamine transport.European journal of pharmacology · 2025Article
- Revealing the location and dynamics of a concealed binding site in the dopamine transporter.Nature communications · 2025Article
- Mechanistic insights of substrate transport and inhibitor binding revealed by high-resolution structures of human norepinephrine transporter.Cell research · 2024Article
- Article
- Effects of SRI-32743, a Novel Quinazoline Structure-Based Compound, on HIV-1 Tat and Cocaine Interaction with Norepinephrine Transporter.International journal of molecular sciences · 2024Article
- Overview of the structure and function of the dopamine transporter and its protein interactions.Frontiers in physiology · 2023Review
- Article
- Non-conserved residues dictate dopamine transporter selectivity for the potent synthetic cathinone and psychostimulant MDPV.Neuropharmacology · 2021Article
- The Role of the Second Extracellular Loop of Norepinephrine Transporter, Neurotrophin-3 and Tropomyosin Receptor Kinase C in T Cells: A Peripheral Biomarker in the Etiology of Schizophrenia.International journal of molecular sciences · 2021Article
- Assessment of Paroxetine Molecular Interactions with Selected Monoamine and γ-Aminobutyric Acid Transporters.International journal of molecular sciences · 2021Article
- Structural basis of norepinephrine recognition and transport inhibition in neurotransmitter transporters.Nature communications · 2021Article
- Paroxetine-Overview of the Molecular Mechanisms of Action.International journal of molecular sciences · 2021Review
- Norepinephrine transporter antagonism prevents dopamine-dependent synaptic plasticity in the mouse dorsal hippocampus.Neuroscience letters · 2021Article
- Norepinephrine transporter-derived homing peptides enable rapid endocytosis of drug delivery nanovehicles into neuroblastoma cells.Journal of nanobiotechnology · 2020Article
- Structure Modeling of the Norepinephrine Transporter.Biomolecules · 2020Article
- Toward a Systematic Structural and Functional Annotation of Solute Carriers Transporters-Example of the SLC6 and SLC7 Families.Frontiers in pharmacology · 2020Review
- Article
- Monoamine Transporter and Receptor Interaction Profiles in Vitro Predict Reported Human Doses of Novel Psychoactive Stimulants and Psychedelics.The international journal of neuropsychopharmacology · 2018Article
- Overview of Monoamine Transporters.Current protocols in pharmacology · 2017Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The transporters for norepinephrine and dopamine (NET and DAT, respectively) constitute the molecular targets for recreational drugs and therapeutics used in the treatment of psychiatric disorders. Despite a strikingly similar amino acid sequence and predicted topology between these transporters, some inhibitors display a high degree of selectivity between NET and DAT. Here, a systematic mutational analysis of non-conserved residues within the extracellular entry pathway and the high affinity binding site in NET and DAT was performed to examine their role for selective inhibitor recognition. Changing the six diverging residues in the central binding site of NET to the complementary residues in DAT transferred a DAT-like pharmacology to NET, showing that non-conserved binding site residues in NET are critical determinants for inhibitor selectivity. In contrast, changing the equivalent residues in the central site of DAT to the corresponding residues in NET had modest effects on the same inhibitors, suggesting that non-conserved binding site residues in DAT play a minor role for selective inhibitor recognition. Our data points towards distinct structural determinants governing inhibitor selectivity in NET and DAT, and provide important new insight into the molecular basis for NET/DAT selectivity of therapeutic and recreational drugs.
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