2W8F

Aplysia californica AChBP bound to in silico compound 31

2W8F の概要

• エントリーDOI: 10.2210/pdb2w8f/pdb
• 関連するPDBエントリー: 2BR7 2BR8 2BYN 2BYP 2BYQ 2BYR 2BYS 2C9T 2UZ6 2W8E 2W8G
• 分子名称: SOLUBLE ACETYLCHOLINE RECEPTOR, (3-EXO)-3-(10,11-DIHYDRO-5H-DIBENZO[A,D][7]ANNULEN-5-YLOXY)-8,8-DIMETHYL-8-AZONIABICYCLO[3.2.1]OCTANE (3 entities in total)
• 機能のキーワード: receptor, acetylcholine receptor inhibitor, acetylcholine binding protein, postsynaptic neurotoxin, nicotinic acetylcholine receptor-toxin complex, neurotoxin, toxin, amidation, conotoxin
• 由来する生物種: APLYSIA CALIFORNICA (CALIFORNIA SEA HARE)
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 247582.78

構造登録者

Ulens, C.,Akdemir, A.,Jongejan, A.,van Elk, R.,Edink, E.,Bertrand, S.,Perrakis, A.,Leurs, R.,Smit, A.B.,Sixma, T.K.,Bertrand, D.,de Esch, I.J. (登録日: 2009-01-16, 公開日: 2009-04-14, 最終更新日: 2024-10-23)

主引用文献

Ulens, C.,Akdemir, A.,Jongejan, A.,Van Elk, R.,Bertrand, S.,Perrakis, A.,Leurs, R.,Smit, A.B.,Sixma, T.K.,Bertrand, D.,De Esch, I.J.
Use of Acetylcholine Binding Protein in the Search for Novel Alpha7 Nicotinic Receptor Ligands. In Silico Docking, Pharmacological Screening, and X- Ray Analysis.
J.Med.Chem., 52:2372-, 2009

PubMed Abstract: Acetylcholine binding protein (AChBP) is widely considered as a functional and structural homologue of the ligand binding domain of Cys-loop receptors. We report the use of AChBP as template to identify ligands for the nicotinic receptors (nAChRs). An in silico screening protocol was set up and applied to crystal structures of AChBP. Several ligands containing a dibenzosuberyl moiety were identified and shown to bind with high affinity to AChBP and alpha7 nAChRs. Two high affinity ligands were cocrystallized with AChBP, revealing the binding mode in the orthosteric site. Functional studies revealed that these two ligands caused inhibition of the alpha7, alpha4beta2, and 5HT(3) receptors. The noncompetive blockade of the receptors suggests that these compounds act by steric hindrance of the channel. The analysis of the dual binding mode of these dibenzosuberyl-containing compounds can lead to better understanding of the complex mode of action of similar tricyclic ligands on Cys-loop receptors.

PubMed: 19331415
DOI: 10.1021/JM801400G

実験手法

X-RAY DIFFRACTION (2.7 Å)