ArticleNature communications2021
Structural basis of norepinephrine recognition and transport inhibition in neurotransmitter transporters.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 57 citations in OpenAlex.
- Multiscale structural connectome eigenmodes constrain human brain functional dynamics.Communications biology · 2026Article
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- Cholecystokinin-expressing GABA neurons elicit long-term potentiation in the cortical inhibitory synapses and attenuate sound-shock associative memory.Scientific reports · 2025Article
- Macromolecular crystallography at Elettra: current and future perspectives.Journal of synchrotron radiation · 2025Article
- Machine Learning Tool for New Selective Serotonin and Serotonin-Norepinephrine Reuptake Inhibitors.Molecules (Basel, Switzerland) · 2025Article
- Novel Ways of Targeting the Dopamine Transporter.Advances in neurobiology · 2025Review
- Pharmacological Mechanisms of SLC6 Neurotransmitter Transporter Inhibition.Advances in neurobiology · 2025Review
- Mechanistic insights of substrate transport and inhibitor binding revealed by high-resolution structures of human norepinephrine transporter.Cell research · 2024Article
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- Structural Studies of the Taurine Transporter: A Potential Biological Target from the GABA Transporter Subfamily in Cancer Therapy.International journal of molecular sciences · 2024Article
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- Serotonin Signaling through Lipid Membranes.ACS chemical neuroscience · 2024Review
- Allosteric modulation of serotonin and dopamine transporters: New insights from computations and experiments.Current research in physiology · 2024Article
- Chirality Matters: Fine-Tuning of Novel Monoamine Reuptake Inhibitors Selectivity through Manipulation of Stereochemistry.Biomolecules · 2023Article
- Cryo-EM structure of GABA transporter 1 reveals substrate recognition and transport mechanism.Nature structural & molecular biology · 2023Article
- Proteochemometric Modeling Identifies Chemically Diverse Norepinephrine Transporter Inhibitors.Journal of chemical information and modeling · 2023Article
- Two-photon fluorescence imaging and specifically biosensing of norepinephrine on a 100-ms timescale.Nature communications · 2023Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Norepinephrine is a biogenic amine neurotransmitter that has widespread effects on alertness, arousal and pain sensation. Consequently, blockers of norepinephrine uptake have served as vital tools to treat depression and chronic pain. Here, we employ the Drosophila melanogaster dopamine transporter as a surrogate for the norepinephrine transporter and determine X-ray structures of the transporter in its substrate-free and norepinephrine-bound forms. We also report structures of the transporter in complex with inhibitors of chronic pain including duloxetine, milnacipran and a synthetic opioid, tramadol. When compared to dopamine, we observe that norepinephrine binds in a different pose, in the vicinity of subsite C within the primary binding site. Our experiments reveal that this region is the binding site for chronic pain inhibitors and a determinant for norepinephrine-specific reuptake inhibition, thereby providing a paradigm for the design of specific inhibitors for catecholamine neurotransmitter transporters.
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