EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Dopamine reuptake and inhibitory mechanisms in human dopamine transporter.
ジャーナル・号・ページ	Nature, Vol. 632, Issue 8025, Page 686-694, Year 2024
掲載日	2024年8月7日
著者	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 要旨	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.
リンク	Nature / PubMed:39112701
手法	EM (単粒子)
解像度	2.8 - 3.16 Å
構造データ	38850 8y2c EMDB-38850, PDB-8y2c: Cryo-EM structure of human dopamine transporter in apo state 手法: EM (単粒子) / 解像度: 3.16 Å 38851 8y2d EMDB-38851, PDB-8y2d: Cryo-EM structure of human dopamine transporter in complex with dopamine 手法: EM (単粒子) / 解像度: 2.8 Å 38852 8y2e EMDB-38852, PDB-8y2e: Cryo-EM structure of human dopamine transporter in complex with benztropine 手法: EM (単粒子) / 解像度: 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 手法: EM (単粒子) / 解像度: 2.97 Å 38854 8y2g EMDB-38854, PDB-8y2g: Cryo-EM structure of human dopamine transporter in complex with methylphenidate 手法: EM (単粒子) / 解像度: 2.83 Å
化合物	ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose / N-アセチル-β-D-グルコサミン ChemComp-LDP: L-DOPAMINE / ド-パミン / 薬剤YM ChemComp-NA: Unknown entry / ナトリウムカチオン ChemComp-CL: Unknown entry / クロリド ChemComp-HOH: WATER ChemComp-CXQ: benztropine / ベンズトロピン / 薬剤, 抗精神病薬YM PDB-1d5s: CRYSTAL STRUCTURE OF CLEAVED ANTITRYPSIN POLYMER PDB-1d5u: Unknown entry
由来	homo sapiens (ヒト)
キーワード	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