4AFT

Aplysia californica AChBP in complex with Varenicline

4AFT の概要

• エントリーDOI: 10.2210/pdb4aft/pdb
• 関連するPDBエントリー: 2BR7 2BR8 2BYN 2BYP 2BYQ 2BYR 2BYS 2C9T 2UZ6 2W8F 2W8G 2WN9 2WNC 2WNJ 2WNL 2WZY 2X00 2XNT 2XNU 2XNV 2XYS 2XYT 2XZ5 2XZ6 2Y54 2Y56 2Y57 2Y58 2Y7Y 4AFO 4AFW
• 分子名称: SOLUBLE ACETYLCHOLINE RECEPTOR, VARENICLINE (2 entities in total)
• 機能のキーワード: receptor protein, nicotinic
• 由来する生物種: APLYSIA CALIFORNICA (CALIFORNIA SEA HARE)
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 124499.20

構造登録者

Rucktooa, P.,Haseler, C.A.,vanElke, R.,Smit, A.B.,Gallagher, T.,Sixma, T.K. (登録日: 2012-01-23, 公開日: 2012-05-02, 最終更新日: 2023-12-20)

主引用文献

Rucktooa, P.,Haseler, C.A.,Van Elk, R.,Smit, A.B.,Gallagher, T.,Sixma, T.K.
Structural Characterization of Binding Mode of Smoking Cessation Drugs to Nicotinic Acetylcholine Receptors Through Study of Ligand Complexes with Acetylcholine-Binding Protein.
J.Biol.Chem., 287:23283-, 2012

PubMed Abstract: Smoking cessation is an important aim in public health worldwide as tobacco smoking causes many preventable deaths. Addiction to tobacco smoking results from the binding of nicotine to nicotinic acetylcholine receptors (nAChRs) in the brain, in particular the α4β2 receptor. One way to aid smoking cessation is by the use of nicotine replacement therapies or partial nAChR agonists like cytisine or varenicline. Here we present the co-crystal structures of cytisine and varenicline in complex with Aplysia californica acetylcholine-binding protein and use these as models to investigate binding of these ligands binding to nAChRs. This analysis of the binding properties of these two partial agonists provides insight into differences with nicotine binding to nAChRs. A mutational analysis reveals that the residues conveying subtype selectivity in nAChRs reside on the binding site complementary face and include features extending beyond the first shell of contacting residues.

PubMed: 22553201
DOI: 10.1074/JBC.M112.360347

実験手法

X-RAY DIFFRACTION (3.2 Å)