5DYY

Crystal structure of human butyrylcholinesterase in complex with N-((1-benzylpiperidin-3-yl)methyl)naphthalene-2-sulfonamide

5DYY の概要

• エントリーDOI: 10.2210/pdb5dyy/pdb
• 分子名称: Cholinesterase, 2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-L-fucopyranose-(1-6)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (11 entities in total)
• 機能のキーワード: hydrolase, human butyrylcholinesterase ad alzheimer disease sulfonamide
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 125771.11

構造登録者

Coquelle, N.,Brus, B.,Colletier, J.P. (登録日: 2015-09-25, 公開日: 2017-01-18, 最終更新日: 2024-10-16)

主引用文献

Kosak, U.,Brus, B.,Knez, D.,Sink, R.,Zakelj, S.,Trontelj, J.,Pislar, A.,Slenc, J.,Gobec, M.,Zivin, M.,Tratnjek, L.,Perse, M.,Saat, K.,Podkowa, A.,Filipek, B.,Nachon, F.,Brazzolotto, X.,Wieckowska, A.,Malawska, B.,Stojan, J.,Rascan, I.M.,Kos, J.,Coquelle, N.,Colletier, J.P.,Gobec, S.
Development of an in-vivo active reversible butyrylcholinesterase inhibitor.
Sci Rep, 6:39495-39495, 2016

PubMed Abstract: Alzheimer's disease (AD) is characterized by severe basal forebrain cholinergic deficit, which results in progressive and chronic deterioration of memory and cognitive functions. Similar to acetylcholinesterase, butyrylcholinesterase (BChE) contributes to the termination of cholinergic neurotransmission. Its enzymatic activity increases with the disease progression, thus classifying BChE as a viable therapeutic target in advanced AD. Potent, selective and reversible human BChE inhibitors were developed. The solved crystal structure of human BChE in complex with the most potent inhibitor reveals its binding mode and provides the molecular basis of its low nanomolar potency. Additionally, this compound is noncytotoxic and has neuroprotective properties. Furthermore, this inhibitor moderately crosses the blood-brain barrier and improves memory, cognitive functions and learning abilities of mice in a model of the cholinergic deficit that characterizes AD, without producing acute cholinergic adverse effects. Our study provides an advanced lead compound for developing drugs for alleviating symptoms caused by cholinergic hypofunction in advanced AD.

PubMed: 28000737
DOI: 10.1038/srep39495

実験手法

X-RAY DIFFRACTION (2.65 Å)