3I6M

3D Structure of Torpedo californica acetylcholinesterase complexed with N-piperidinopropyl-galanthamine

3I6M の概要

• エントリーDOI: 10.2210/pdb3i6m/pdb
• 関連するPDBエントリー: 1DX6 1QTI 1W4L 1W6R 1W76 3I6Z
• 分子名称: Acetylcholinesterase, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• 機能のキーワード: serine hydrolase, cholinesterase, neurotransmitter degradation, alzheimer's disease, bis-functional galanthamine derivative, alternative splicing, cell junction, cell membrane, disulfide bond, glycoprotein, gpi-anchor, hydrolase, lipoprotein, membrane, serine esterase, synapse
• 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: 61491.36

構造登録者

Lamba, D.,Bartolucci, C. (登録日: 2009-07-07, 公開日: 2010-01-12, 最終更新日: 2023-09-06)

主引用文献

Bartolucci, C.,Haller, L.A.,Jordis, U.,Fels, G.,Lamba, D.
Probing Torpedo californica acetylcholinesterase catalytic gorge with two novel bis-functional galanthamine derivatives.
J.Med.Chem., 53:745-751, 2010

PubMed Abstract: N-Piperidinopropyl-galanthamine (2) and N-saccharinohexyl-galanthamine (3) were used to investigate interaction sites along the active site gorge of Torpedo californica actylcholinesterase (TcAChE). The crystal structure of TcAChE-2 solved at 2.3 A showed that the N-piperidinopropyl group in 2 is not stretched along the gorge but is folded over the galanthamine moiety. This result was unexpected because the three carbon alkyl chain is just long enough for the bulky piperidine group to be placed above the bottleneck (Tyr121, Phe330) midway down the gorge. The crystal structure of TcAChE-3 at 2.2 A confirmed that a dual interaction with the sites at the bottom, and at the entrance of the gorge, enhances inhibitory activity: a chain of six carbon atoms has, in this class of derivatives, the correct length for optimal interactions with the peripheral anionic site (PAS).

PubMed: 20025280
DOI: 10.1021/jm901296p

実験手法

X-RAY DIFFRACTION (2.26 Å)