2X8B
Crystal structure of human acetylcholinesterase inhibited by aged tabun and complexed with fasciculin-II
2X8B の概要
| エントリーDOI | 10.2210/pdb2x8b/pdb |
| 関連するPDBエントリー | 1B41 1F8U 1FSC 1FSS 1KU6 1MAH 1PUV 1PUW 1VZJ 2CLJ |
| 分子名称 | ACETHYLCHOLINESTERASE, FASCICULIN-2, CHLORIDE ION, ... (7 entities in total) |
| 機能のキーワード | hydrolase-toxin complex, cell junction, hydrolase, gpi-anchor, neurotransmitter degradation, tabun, aging, serine esterase, blood group antigen, hydrolase/toxin |
| 由来する生物種 | HOMO SAPIENS (HUMAN) 詳細 |
| タンパク質・核酸の鎖数 | 2 |
| 化学式量合計 | 72446.02 |
| 構造登録者 | |
| 主引用文献 | Carletti, E.,Colletier, J.P.,Dupeux, F.,Trovaslet, M.,Masson, P.,Nachon, F. Structural evidence that human acetylcholinesterase inhibited by tabun ages through O-dealkylation. J. Med. Chem., 53:4002-4008, 2010 Cited by PubMed Abstract: Tabun is a warfare agent that inhibits human acetylcholinesterase (hAChE) by rapid phosphylation of the catalytic serine. A time-dependent reaction occurs on the tabun adduct, leading to an "aged" enzyme, resistant to oxime reactivators. The aging reaction may proceed via either dealkylation or deamidation, depending on the stereochemistry of the phosphoramidyl adduct. We solved the X-ray structure of aged tabun-hAChE complexed with fasciculin II, and we show that aging proceeds through O-dealkylation, in agreement with the aging mechanism that we determined for tabun-inhibited human butyrylcholinesterase and mouse acetylcholinesterase. Noteworthy, aging and binding of fasciculin II lead to an improved thermostability, resulting from additional stabilizing interactions between the two subdomains that face each other across the active site gorge. This first structure of hAChE inhibited by a nerve agent provides structural insight into the inhibition and aging mechanisms and a structural template for the design of molecules capable of reactivating aged hAChE. PubMed: 20408548DOI: 10.1021/jm901853b 主引用文献が同じPDBエントリー |
| 実験手法 | X-RAY DIFFRACTION (2.95 Å) |
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