Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Molecular basis of human noradrenaline transporter reuptake and inhibition.
Journal, issue, pages	Nature, Vol. 632, Issue 8026, Page 921-929, Year 2024
Publish date	Jul 24, 2024
Authors	Jiaxin Tan / Yuan Xiao / Fang Kong / Xiaochun Zhang / Hanwen Xu / Angqi Zhu / Yiming Liu / Jianlin Lei / Boxue Tian / Yafei Yuan / Chuangye Yan /
PubMed Abstract	Noradrenaline, also known as norepinephrine, has a wide range of activities and effects on most brain cell types. Its reuptake from the synaptic cleft heavily relies on the noradrenaline transporter ...Noradrenaline, also known as norepinephrine, has a wide range of activities and effects on most brain cell types. Its reuptake from the synaptic cleft heavily relies on the noradrenaline transporter (NET) located in the presynaptic membrane. Here we report the cryo-electron microscopy (cryo-EM) structures of the human NET in both its apo state and when bound to substrates or antidepressant drugs, with resolutions ranging from 2.5 Å to 3.5 Å. The two substrates, noradrenaline and dopamine, display a similar binding mode within the central substrate binding site (S1) and within a newly identified extracellular allosteric site (S2). Four distinct antidepressants, namely, atomoxetine, desipramine, bupropion and escitalopram, occupy the S1 site to obstruct substrate transport in distinct conformations. Moreover, a potassium ion was observed within sodium-binding site 1 in the structure of the NET bound to desipramine under the KCl condition. Complemented by structural-guided biochemical analyses, our studies reveal the mechanism of substrate recognition, the alternating access of NET, and elucidate the mode of action of the four antidepressants.
External links	Nature / PubMed:39048818
Methods	EM (single particle)
Resolution	2.5 - 3.47 Å
Structure data	34718 8hfe EMDB-34718, PDB-8hfe: Cryo-EM structure of human norepinephrine transporter NET in an inward-open state at resolution of 2.5 angstrom Method: EM (single particle) / Resolution: 2.5 Å 34719 8hff EMDB-34719, PDB-8hff: Cryo-EM structure of human norepinephrine transporter NET in the presence of norepinephrine in an inward-open state at resolution of 2.9 angstrom. Method: EM (single particle) / Resolution: 2.86 Å 34720 8hfg EMDB-34720, PDB-8hfg: Cryo-EM structure of human norepinephrine transporter NET in the presence of dopamine in an inward-open state at resolution of 3.0 angstrom. Method: EM (single particle) / Resolution: 3.0 Å 34721 8hfi EMDB-34721, PDB-8hfi: Cryo-EM structure of human norepinephrine transporter NET in the presence of the antidepressant desipramine in an inward-open state at resolution of 2.5 angstrom. Method: EM (single particle) / Resolution: 2.5 Å 34722 8hfl EMDB-34722, PDB-8hfl: Cryo-EM structure of human norepinephrine transporter NET in the presence of the antidepressant bupropion in an inward-open state at resolution of 3.0 angstrom. Method: EM (single particle) / Resolution: 3.0 Å 35157 8i3v EMDB-35157, PDB-8i3v: Cryo-EM structure of human norepinephrine transporter NET in the presence of the antidepressant escitalopram in an inward-open state at resolution of 2.85 angstrom. Method: EM (single particle) / Resolution: 2.85 Å 37515 8wgr EMDB-37515, PDB-8wgr: Cryo-EM structure of inward-open state human norepinephrine transporter NET bound with antidepressant desipramine in KCl condition. Method: EM (single particle) / Resolution: 2.75 Å 37520 8wgx EMDB-37520, PDB-8wgx: Cryo-EM structure of inward-open state human norepinephrine transporter NET bound with norepinephrine in nanodisc. Method: EM (single particle) / Resolution: 3.47 Å 39729 8z1l EMDB-39729, PDB-8z1l: Cryo-EM structure of human norepinephrine transporter NET in the presence of the antidepressant atomoxetine in an outward-open state at resolution of 3.4 angstrom. Method: EM (single particle) / Resolution: 3.4 Å
Chemicals	ChemComp-CL: Unknown entry ChemComp-HOH: WATER ChemComp-LNR: L-NOREPINEPHRINE / neurotransmitter, hormoneYM ChemComp-LDP: L-DOPAMINE / medicationYM ChemComp-DSM: 3-(10,11-DIHYDRO-5H-DIBENZO[B,F]AZEPIN-5-YL)-N-METHYLPROPAN-1-AMINE / antidepressant, inhibitorYM ChemComp, No image ChemComp-1XR: Unknown entry ChemComp-68P: (1S)-1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-2-benzofuran-5-carbonitrile / antidepressant, inhibitorYM ChemComp-K: Unknown entry PDB Unreleased entry PDB-1lx4: Solution NMR Structure Of E. coli N-Ada/DNA transcription complex
Source	homo sapiens (human)
Keywords	TRANSPORT PROTEIN / Norepinephrine transporter / NET / SLC6A2 / norepinephrine / dopamine / neurotransmitter / desipramine / bupropion / antidepressant. / MEMBRANE PROTEIN / escitalopram / inward-open / atomoxetine