Loading
PDBj
メニューPDBj@FacebookPDBj@X(formerly Twitter)PDBj@BlueSkyPDBj@YouTubewwPDB FoundationwwPDBDonate
RCSB PDBPDBeBMRBAdv. SearchSearch help

8Y2G

Cryo-EM structure of human dopamine transporter in complex with methylphenidate

これはPDB形式変換不可エントリーです。
8Y2G の概要
エントリーDOI10.2210/pdb8y2g/pdb
EMDBエントリー38854
分子名称Sodium-dependent dopamine transporter, Dexmethylphenidate, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
機能のキーワードhuman dopamine transporter in complex with methylphenidate, membrane protein
由来する生物種Homo sapiens (human)
タンパク質・核酸の鎖数1
化学式量合計63208.58
構造登録者
Zhao, Y.,Li, Y. (登録日: 2024-01-25, 公開日: 2024-08-14, 最終更新日: 2024-11-20)
主引用文献Li, Y.,Wang, X.,Meng, Y.,Hu, T.,Zhao, J.,Li, R.,Bai, Q.,Yuan, P.,Han, J.,Hao, K.,Wei, Y.,Qiu, Y.,Li, N.,Zhao, Y.
Dopamine reuptake and inhibitory mechanisms in human dopamine transporter.
Nature, 632:686-694, 2024
Cited by
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. 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.
PubMed: 39112701
DOI: 10.1038/s41586-024-07796-0
主引用文献が同じPDBエントリー
実験手法
ELECTRON MICROSCOPY (2.83 Å)
構造検証レポート
Validation report summary of 8y2g
検証レポート(詳細版)ダウンロードをダウンロード

238895

件を2025-07-16に公開中

PDB statisticsPDBj update infoContact PDBjnumon