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	Transport and inhibition mechanisms of the human noradrenaline transporter.
Journal, issue, pages	Nature, Vol. 632, Issue 8026, Page 930-937, Year 2024
Publish date	Jul 31, 2024
Authors	Tuo Hu / Zhuoya Yu / Jun Zhao / Yufei Meng / Kristine Salomon / Qinru Bai / Yiqing Wei / Jinghui Zhang / Shujing Xu / Qiuyun Dai / Rilei Yu / Bei Yang / Claus J Loland / Yan Zhao /
PubMed Abstract	The noradrenaline transporter (also known as norepinephrine transporter) (NET) has a critical role in terminating noradrenergic transmission by utilizing sodium and chloride gradients to drive the ...The noradrenaline transporter (also known as norepinephrine transporter) (NET) has a critical role in terminating noradrenergic transmission by utilizing sodium and chloride gradients to drive the reuptake of noradrenaline (also known as norepinephrine) into presynaptic neurons. It is a pharmacological target for various antidepressants and analgesic drugs. Despite decades of research, its structure and the molecular mechanisms underpinning noradrenaline transport, coupling to ion gradients and non-competitive inhibition remain unknown. Here we present high-resolution complex structures of NET in two fundamental conformations: in the apo state, and bound to the substrate noradrenaline, an analogue of the χ-conotoxin MrlA (χ-MrlA), bupropion or ziprasidone. The noradrenaline-bound structure clearly demonstrates the binding modes of noradrenaline. The coordination of Na and Cl undergoes notable alterations during conformational changes. Analysis of the structure of NET bound to χ-MrlA provides insight into how conotoxin binds allosterically and inhibits NET. Additionally, bupropion and ziprasidone stabilize NET in its inward-facing state, but they have distinct binding pockets. These structures define the mechanisms governing neurotransmitter transport and non-competitive inhibition in NET, providing a blueprint for future drug design.
External links	Nature / PubMed:39085602
Methods	EM (single particle)
Resolution	2.7 - 3.2 Å
Structure data	37842 8wtu EMDB-37842, PDB-8wtu: Cryo-EM structure of noradrenaline transporter in apo state Method: EM (single particle) / Resolution: 2.7 Å 37843 8wtv EMDB-37843, PDB-8wtv: Cryo-EM structure of noradrenaline transporter in complex with noradrenaline Method: EM (single particle) / Resolution: 2.7 Å 37844 8wtw EMDB-37844, PDB-8wtw: Cryo-EM structure of noradrenaline transporter in complex with a x-MrlA analogue Method: EM (single particle) / Resolution: 2.8 Å 37845 8wtx EMDB-37845, PDB-8wtx: Cryo-EM structure of noradrenaline transporter in complex with bupropion Method: EM (single particle) / Resolution: 2.9 Å 37846 8wty EMDB-37846, PDB-8wty: Cryo-EM structure of noradrenaline transporter in complex with ziprasidone Method: EM (single particle) / Resolution: 3.2 Å
Chemicals	ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose ChemComp-NA: Unknown entry ChemComp-CL: Unknown entry ChemComp-E5E: Noradrenaline / neurotransmitter, hormoneYM ChemComp-HOH: WATER ChemComp, No image ChemComp-Y60: Unknown entry ChemComp, No image ChemComp-XEF*: Unknown entry
Source	homo sapiens (human) conus marmoreus (invertebrata)
Keywords	STRUCTURAL PROTEIN / protein structure / Norapinephrine transporter / MrlA / noradrenaline transporter / inhibition / bupropion / Ziprasidone