6G1U

Crystal structure of Torpedo Californica acetylcholinesterase in complex with 9-Amino-6-chloro-1,2,3,4-tetrahydro-10-methylacridin-10-ium

「6FOT」から置き換えられました

6G1U の概要

• エントリーDOI: 10.2210/pdb6g1u/pdb
• 分子名称: Acetylcholinesterase, 2-acetamido-2-deoxy-beta-D-glucopyranose, DI(HYDROXYETHYL)ETHER, ... (6 entities in total)
• 機能のキーワード: torpedo californica acetylcholinesterase, ad, alzheimer disease, hydrolase
• 由来する生物種: Tetronarce californica (Pacific electric ray)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 131907.53

構造登録者

Coquelle, N.,Colletier, J.P. (登録日: 2018-03-22, 公開日: 2018-04-04, 最終更新日: 2024-11-13)

主引用文献

Galdeano, C.,Coquelle, N.,Cieslikiewicz-Bouet, M.,Bartolini, M.,Perez, B.,Clos, M.V.,Silman, I.,Jean, L.,Colletier, J.P.,Renard, P.Y.,Munoz-Torrero, D.
Increasing Polarity in Tacrine and Huprine Derivatives: Potent Anticholinesterase Agents for the Treatment of Myasthenia Gravis.
Molecules, 23:-, 2018

PubMed Abstract: Symptomatic treatment of myasthenia gravis is based on the use of peripherally-acting acetylcholinesterase (AChE) inhibitors that, in some cases, must be discontinued due to the occurrence of a number of side-effects. Thus, new AChE inhibitors are being developed and investigated for their potential use against this disease. Here, we have explored two alternative approaches to get access to peripherally-acting AChE inhibitors as new agents against myasthenia gravis, by structural modification of the brain permeable anti-Alzheimer AChE inhibitors tacrine, 6-chlorotacrine, and huprine Y. Both quaternization upon methylation of the quinoline nitrogen atom, and tethering of a triazole ring, with, in some cases, the additional incorporation of a polyphenol-like moiety, result in more polar compounds with higher inhibitory activity against human AChE (up to 190-fold) and butyrylcholinesterase (up to 40-fold) than pyridostigmine, the standard drug for symptomatic treatment of myasthenia gravis. The novel compounds are furthermore devoid of brain permeability, thereby emerging as interesting leads against myasthenia gravis.

PubMed: 29534488
DOI: 10.3390/molecules23030634

実験手法

X-RAY DIFFRACTION (1.79 Å)