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	Dopamine reuptake and inhibitory mechanisms in human dopamine transporter.
Journal, issue, pages	Nature, Vol. 632, Issue 8025, Page 686-694, Year 2024
Publish date	Aug 7, 2024
Authors	Yue Li / Xianping Wang / Yufei Meng / Tuo Hu / Jun Zhao / Renjie Li / Qinru Bai / Pu Yuan / Jun Han / Kun Hao / Yiqing Wei / Yunlong Qiu / Na Li / Yan Zhao /
PubMed Abstract	The dopamine transporter has a crucial role in regulation of dopaminergic neurotransmission by uptake of dopamine into neurons and contributes to the abuse potential of psychomotor stimulants. ...The dopamine transporter has a crucial role in regulation of dopaminergic neurotransmission by uptake of dopamine into neurons and contributes to the abuse potential of psychomotor stimulants. Despite decades of study, the structure, substrate binding, conformational transitions and drug-binding poses of human dopamine transporter remain unknown. Here we report structures of the human dopamine transporter in its apo state, and in complex with the substrate dopamine, the attention deficit hyperactivity disorder drug methylphenidate, and the dopamine-uptake inhibitors GBR12909 and benztropine. The dopamine-bound structure in the occluded state precisely illustrates the binding position of dopamine and associated ions. The structures bound to drugs are captured in outward-facing or inward-facing states, illuminating distinct binding modes and conformational transitions during substrate transport. Unlike the outward-facing state, which is stabilized by cocaine, GBR12909 and benztropine stabilize the dopamine transporter in the inward-facing state, revealing previously unseen drug-binding poses and providing insights into how they counteract the effects of cocaine. This study establishes a framework for understanding the functioning of the human dopamine transporter and developing therapeutic interventions for dopamine transporter-related disorders and cocaine addiction.
External links	Nature / PubMed:39112701
Methods	EM (single particle)
Resolution	2.8 - 3.16 Å
Structure data	38850 8y2c EMDB-38850, PDB-8y2c: Cryo-EM structure of human dopamine transporter in apo state Method: EM (single particle) / Resolution: 3.16 Å 38851 8y2d EMDB-38851, PDB-8y2d: Cryo-EM structure of human dopamine transporter in complex with dopamine Method: EM (single particle) / Resolution: 2.8 Å 38852 8y2e EMDB-38852, PDB-8y2e: Cryo-EM structure of human dopamine transporter in complex with benztropine Method: EM (single particle) / Resolution: 3.03 Å 38853 8y2f EMDB-38853: structure of a proteinACryo-EM structure of human dopamine transporter in complex with GBR12909 PDB-8y2f: Cryo-EM structure of human dopamine transporter in complex with GBR12909 Method: EM (single particle) / Resolution: 2.97 Å 38854 8y2g EMDB-38854, PDB-8y2g: Cryo-EM structure of human dopamine transporter in complex with methylphenidate Method: EM (single particle) / Resolution: 2.83 Å
Chemicals	ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose ChemComp-LDP: L-DOPAMINE / medicationYM ChemComp-NA: Unknown entry ChemComp-CL: Unknown entry ChemComp-HOH: WATER ChemComp-CXQ: benztropine / medication, antipsychoticYM PDB-1d5s: CRYSTAL STRUCTURE OF CLEAVED ANTITRYPSIN POLYMER PDB-1d5u: Unknown entry
Source	homo sapiens (human)
Keywords	MEMBRANE PROTEIN / human dopamine transporter in apo state / human dopamine transporter in complex with dopamine / human dopamine transporter in complex with benztropine / human dopamine transporter human dopamine transporter / human dopamine transporter in complex with methylphenidate