1QTI

Acetylcholinesterase (E.C.3.1.1.7)

1QTI の概要

• エントリーDOI: 10.2210/pdb1qti/pdb
• 関連するPDBエントリー: 1ACJ 1ACL 1AMN 1CFJ 1EVE 1OCE 1VOT 2ACE 2ACK
• 分子名称: ACETYLCHOLINESTERASE, (-)-GALANTHAMINE (3 entities in total)
• 機能のキーワード: alzheimer's disease, drug, serine hydrolase, alpha/beta hydrolase, neurotransmitter cleaveage, catalytic triad, hydrolase
• 由来する生物種: Torpedo californica (Pacific electric ray)
• 細胞内の位置: Isoform H: Cell membrane; Lipid-anchor, GPI- anchor. Isoform T: Cell membrane; Peripheral membrane protein: P04058
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 61023.87

構造登録者

Bartolucci, C.,Perola, E.,Pilger, C.,Fels, G.,Lamba, D. (登録日: 1999-06-28, 公開日: 1999-12-29, 最終更新日: 2024-10-09)

主引用文献

Bartolucci, C.,Perola, E.,Pilger, C.,Fels, G.,Lamba, D.
Three-dimensional structure of a complex of galanthamine (Nivalin) with acetylcholinesterase from Torpedo californica: implications for the design of new anti-Alzheimer drugs
Proteins, 42:182-191, 2001

PubMed Abstract: The 3D structure of a complex of the anti-Alzheimer drug galanthamine with Torpedo californica acetylcholinesterase is reported. Galanthamine, a tertiary alkaloid extracted from several species of Amarylidacae, is so far the only drug that shows a dual activity, being both an acetylcholinesterase inhibitor and an allosteric potentiator of the nicotinic response induced by acetylcholine and competitive agonists. The X-ray structure, at 2.5A resolution, shows an unexpected orientation of the ligand within the active site, as well as unusual protein-ligand interactions. The inhibitor binds at the base of the active site gorge, interacting with both the acyl-binding pocket and the principal quaternary ammonium-binding site. However, the tertiary amine group of galanthamine does not directly interact with Trp84. A docking study using the program AUTODOCK correctly predicts the orientation of galanthamine in the active site. The docked lowest-energy structure has a root mean square deviation of 0.5A with respect to the corresponding crystal structure of the complex. The observed binding mode explains the affinities of a series of structural analogs of galanthamine and provides a rational basis for structure-based drug design of synthetic derivatives with improved pharmacological properties. Proteins 2001;42:182-191.

PubMed: 11119642
DOI: 10.1002/1097-0134(20010201)42:2<182::AID-PROT50>3.0.CO;2-1

実験手法

X-RAY DIFFRACTION (2.5 Å)