6IQL

Crystal structure of dopamine receptor D4 bound to the subtype-selective ligand, L745870

6IQL の概要

• エントリーDOI: 10.2210/pdb6iql/pdb
• 分子名称: D(4) dopamine receptor,Soluble cytochrome b562,D(4) dopamine receptor, 3-{[4-(4-chlorophenyl)piperazin-1-yl]methyl}-1H-pyrrolo[2,3-b]pyridine (2 entities in total)
• 機能のキーワード: gpcr, drd4, l745870, ligand, dimerization, signaling protein
• 由来する生物種: Mus musculus (Mouse); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 87785.01

構造登録者

Zhou, Y.,Cao, C.,Zhang, X.C. (登録日: 2018-11-08, 公開日: 2019-12-04, 最終更新日: 2024-11-13)

主引用文献

Zhou, Y.,Cao, C.,He, L.,Wang, X.,Zhang, X.C.
Crystal structure of dopamine receptor D4 bound to the subtype selective ligand, L745870.
Elife, 8:-, 2019

PubMed Abstract: Multiple subtypes of dopamine receptors within the GPCR superfamily regulate neurological processes through various downstream signaling pathways. A crucial question about the dopamine receptor family is what structural features determine the subtype-selectivity of potential drugs. Here, we report the 3.5-angstrom crystal structure of mouse dopamine receptor D4 (DRD4) complexed with a subtype-selective antagonist, L745870. Our structure reveals a secondary binding pocket extended from the orthosteric ligand-binding pocket to a DRD4-specific crevice located between transmembrane helices 2 and 3. Additional mutagenesis studies suggest that the antagonist L745870 prevents DRD4 activation by blocking the relative movement between transmembrane helices 2 and 3. These results expand our knowledge of the molecular basis for the physiological functions of DRD4 and assist new drug design.

PubMed: 31750832
DOI: 10.7554/eLife.48822

実験手法

X-RAY DIFFRACTION (3.5 Å)