3ZPR

Thermostabilised turkey beta1 adrenergic receptor with 4-methyl-2-(piperazin-1-yl) quinoline bound

3ZPR の概要

• エントリーDOI: 10.2210/pdb3zpr/pdb
• 関連するPDBエントリー: 3ZPQ
• 分子名称: BETA-1 ADRENERGIC RECEPTOR, SODIUM ION, CHOLESTEROL HEMISUCCINATE, ... (6 entities in total)
• 機能のキーワード: membrane protein, gpcr, fragment screening, aryl piperazine, structure based drug design
• 由来する生物種: MELEAGRIS GALLOPAVO (TURKEY)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 77410.94

構造登録者

Christopher, J.A.,Congreve, M.,Dore, A.S.,Marshall, F.H.,Myszka, D.G.,Brown, J.,Koglin, M.,Tehan, B.,Errey, J.C.,Tate, C.G.,Warne, T. (登録日: 2013-03-01, 公開日: 2013-04-03, 最終更新日: 2024-10-23)

主引用文献

Christopher, J.,Brown, J.,Dore, A.,Errey, J.,Koglin, M.,Marshall, F.H.,Myszka, D.,Rich, R.L.,Tate, C.G.,Tehan, B.,Warne, T.,Congreve, M.
Biophysical Fragment Screening of the Beta1-Adrenergic Receptor: Identification of High Affinity Aryl Piperazine Leads Using Structure-Based Drug Design.
J.Med.Chem., 56:3446-, 2013

PubMed Abstract: Biophysical fragment screening of a thermostabilized β1-adrenergic receptor (β1AR) using surface plasmon resonance (SPR) enabled the identification of moderate affinity, high ligand efficiency (LE) arylpiperazine hits 7 and 8. Subsequent hit to lead follow-up confirmed the activity of the chemotype, and a structure-based design approach using protein-ligand crystal structures of the β1AR resulted in the identification of several fragments that bound with higher affinity, including indole 19 and quinoline 20. In the first example of GPCR crystallography with ligands derived from fragment screening, structures of the stabilized β1AR complexed with 19 and 20 were determined at resolutions of 2.8 and 2.7 Å, respectively.

PubMed: 23517028
DOI: 10.1021/JM400140Q

実験手法

X-RAY DIFFRACTION (2.7 Å)