5OV9

Crystal structure of Acetylcholinesterase in complex with Crystal Violet

5OV9 の概要

• エントリーDOI: 10.2210/pdb5ov9/pdb
• 分子名称: Acetylcholinesterase, 2-{2-[2-(2-{2-[2-(2-ETHOXY-ETHOXY)-ETHOXY]-ETHOXY}-ETHOXY)-ETHOXY]-ETHOXY}-ETHANOL, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (11 entities in total)
• 機能のキーワード: dimeric, complex, inhibitor, hydrolase
• 由来する生物種: Mus musculus (Mouse)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 123904.32

構造登録者

Allgardsson, A.,Andersson, C.D.,Akfur, C.,Worek, F.,Linusson, A.,Ekstrom, F. (登録日: 2017-08-28, 公開日: 2017-09-06, 最終更新日: 2024-11-20)

主引用文献

Allgardsson, A.,David Andersson, C.,Akfur, C.,Worek, F.,Linusson, A.,Ekstrom, F.
An Unusual Dimeric Inhibitor of Acetylcholinesterase: Cooperative Binding of Crystal Violet.
Molecules, 22:-, 2017

PubMed Abstract: Acetylcholinesterase (AChE) is an essential enzyme that terminates cholinergic transmission by a rapid hydrolysis of the neurotransmitter acetylcholine. AChE is an important target for treatment of various cholinergic deficiencies, including Alzheimer's disease and myasthenia gravis. In a previous high throughput screening campaign, we identified the dye crystal violet (CV) as an inhibitor of AChE. Herein, we show that CV displays a significant cooperativity for binding to AChE, and the molecular basis for this observation has been investigated by X-ray crystallography. Two monomers of CV bind to residues at the entrance of the active site gorge of the enzyme. Notably, the two CV molecules have extensive intermolecular contacts with each other and with AChE. Computational analyses show that the observed CV dimer is not stable in solution, suggesting the sequential binding of two monomers. Guided by the structural analysis, we designed a set of single site substitutions, and investigated their effect on the binding of CV. Only moderate effects on the binding and the cooperativity were observed, suggesting a robustness in the interaction between CV and AChE. Taken together, we propose that the dimeric cooperative binding is due to a rare combination of chemical and structural properties of both CV and the AChE molecule itself.

PubMed: 28867801
DOI: 10.3390/molecules22091433

実験手法

X-RAY DIFFRACTION (2.4 Å)