4XP9

X-ray structure of Drosophila dopamine transporter bound to psychostimulant D-amphetamine

4XP9 の概要

• エントリーDOI: 10.2210/pdb4xp9/pdb
• 関連するPDBエントリー: 4XNX 4XP1 4XP4 4XP5 4XP6 4XPA 4XPB 4XPF 4XPG 4XPH 4XPT
• 関連するBIRD辞書のPRD_ID: PRD_900001
• 分子名称: Transporter, 1-ETHOXY-2-(2-ETHOXYETHOXY)ETHANE, SODIUM ION, ... (13 entities in total)
• 機能のキーワード: integral membrane protein, all-alpha helical antidepressant complex, membrane protein, protein transport, transport protein-inhibitor complex, transport protein/inhibitor
• 由来する生物種: Drosophila melanogaster (Fruit fly); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 109726.47

構造登録者

Aravind, P.,Wang, K.,Gouaux, E. (登録日: 2015-01-16, 公開日: 2015-05-06, 最終更新日: 2024-10-23)

主引用文献

Wang, K.H.,Penmatsa, A.,Gouaux, E.
Neurotransmitter and psychostimulant recognition by the dopamine transporter.
Nature, 521:322-327, 2015

PubMed Abstract: Na(+)/Cl(-)-coupled biogenic amine transporters are the primary targets of therapeutic and abused drugs, ranging from antidepressants to the psychostimulants cocaine and amphetamines, and to their cognate substrates. Here we determine X-ray crystal structures of the Drosophila melanogaster dopamine transporter (dDAT) bound to its substrate dopamine, a substrate analogue 3,4-dichlorophenethylamine, the psychostimulants d-amphetamine and methamphetamine, or to cocaine and cocaine analogues. All ligands bind to the central binding site, located approximately halfway across the membrane bilayer, in close proximity to bound sodium and chloride ions. The central binding site recognizes three chemically distinct classes of ligands via conformational changes that accommodate varying sizes and shapes, thus illustrating molecular principles that distinguish substrates from inhibitors in biogenic amine transporters.

PubMed: 25970245
DOI: 10.1038/nature14431

実験手法

X-RAY DIFFRACTION (2.8 Å)