2JF0

Mus musculus acetylcholinesterase in complex with tabun and Ortho-7

2JF0 の概要

• エントリーDOI: 10.2210/pdb2jf0/pdb
• 関連するPDBエントリー: 1C2B 1C2O 1J06 1J07 1KU6 1MAA 1MAH 1N5M 1N5R 1Q83 1Q84 2C0P 2C0Q 2H9Y 2HA0 2HA2 2HA3 2HA4 2HA5 2HA6 2HA7 2JEY 2JEZ
• 分子名称: ACETYLCHOLINESTERASE, HEXAETHYLENE GLYCOL, 1,7-HEPTYLENE-BIS-N,N'-SYN-2-PYRIDINIUMALDOXIME, ... (4 entities in total)
• 機能のキーワード: acetylcholinesterase, alternative splicing, neurotransmitter degradation, hydrolase, mus musculus, glycoprotein, serine esterase, oxime, mouse, tabun, synapse, ortho-7, membrane
• 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: 121705.37

構造登録者

Ekstrom, F.,Astot, C.,Pang, Y.P. (登録日: 2007-01-25, 公開日: 2007-07-03, 最終更新日: 2023-12-13)

主引用文献

Ekstrom, F.J.,Astot, C.,Pang, Y.
Novel Nerve-Agent Antidote Design Based on Crystallographic and Mass Spectrometric Analyses of Tabun-Conjugated Acetylcholinesterase in Complex with Antidotes.
Clin.Pharmacol.Ther., 82:282-, 2007

PubMed Abstract: Organophosphorus compound-based nerve agents inhibit the essential enzyme acetylcholinesterase (AChE) causing acute toxicity and death. Clinical treatment of nerve-agent poisoning is to use oxime-based antidotes to reactivate the inhibited AChE. However, the nerve agent tabun is resistant to oximes. To design improved oximes, crystal structures of a tabun-conjugated AChE in complex with different oximes are needed to guide the structural modifications of known antidotes. However, this type of structure is extremely challenging to obtain because both deamidation of the tabun conjugate and reactivation of AChE occur during crystallographic experiments. Here we report, for the first time, the crystal structures of Ortho-7 and HLö-7 in complex with AChE that is conjugated to an intact tabun. These structures were determined by our new strategy of combining crystallographic and mass spectrometric analyses of AChE crystals. The results explain the relative reactivation potencies of the two oximes and offer insights into improving known medical antidotes.

PubMed: 17443135
DOI: 10.1038/SJ.CLPT.6100151

実験手法

X-RAY DIFFRACTION (2.5 Å)