1N5M

Crystal structure of the mouse acetylcholinesterase-gallamine complex

1N5M の概要

• エントリーDOI: 10.2210/pdb1n5m/pdb
• 関連するPDBエントリー: 1J06 1J07 1MAA 1MAH 1N5R
• 分子名称: acetylcholinesterase, alpha-L-fucopyranose-(1-6)-2-acetamido-2-deoxy-beta-D-glucopyranose, IODIDE ION, ... (9 entities in total)
• 機能のキーワード: hydrolase, serine esterase, acetylcholinesterase, homodimer, hydrolase fold, glycosylated protein
• 由来する生物種: Mus musculus (house mouse)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 122089.60

構造登録者

Bourne, Y.,Taylor, P.,Radic, Z.,Marchot, P. (登録日: 2002-11-06, 公開日: 2003-02-04, 最終更新日: 2024-11-06)

主引用文献

Bourne, Y.,Taylor, P.,Radic, Z.,Marchot, P.
Structural insights into ligand interactions at the acetylcholinesterase peripheral anionic site
EMBO J., 22:1-12, 2003

PubMed Abstract: The peripheral anionic site on acetylcholinesterase (AChE), located at the active center gorge entry, encompasses overlapping binding sites for allosteric activators and inhibitors; yet, the molecular mechanisms coupling this site to the active center at the gorge base to modulate catalysis remain unclear. The peripheral site has also been proposed to be involved in heterologous protein associations occurring during synaptogenesis or upon neurodegeneration. A novel crystal form of mouse AChE, combined with spectrophotometric analyses of the crystals, enabled us to solve unique structures of AChE with a free peripheral site, and as three complexes with peripheral site inhibitors: the phenylphenanthridinium ligands, decidium and propidium, and the pyrogallol ligand, gallamine, at 2.20-2.35 A resolution. Comparison with structures of AChE complexes with the peptide fasciculin or with organic bifunctional inhibitors unveils new structural determinants contributing to ligand interactions at the peripheral site, and permits a detailed topographic delineation of this site. Hence, these structures provide templates for designing compounds directed to the enzyme surface that modulate specific surface interactions controlling catalytic activity and non-catalytic heterologous protein associations.

PubMed: 12505979
DOI: 10.1093/emboj/cdg005

実験手法

X-RAY DIFFRACTION (2.2 Å)