6XTA

Recombinant human butyrylcholinesterase in complex with (2S)-N-[2-(1-benzylazepan-4-yl)ethyl]-2-(butylamino)-3-(1H-indol-3-yl)propanamide

6XTA の概要

• エントリーDOI: 10.2210/pdb6xta/pdb
• 分子名称: Cholinesterase, alpha-L-fucopyranose-(1-6)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (9 entities in total)
• 機能のキーワード: butyrylcholinesterase, inhibitor, complex, hydrolase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 62587.83

構造登録者

Brazzolotto, X.,Nachon, F.,Meden, A.,Knez, D.,Gobec, S. (登録日: 2020-01-15, 公開日: 2020-10-28, 最終更新日: 2024-10-16)

主引用文献

Meden, A.,Knez, D.,Malikowska-Racia, N.,Brazzolotto, X.,Nachon, F.,Svete, J.,Salat, K.,Groselj, U.,Gobec, S.
Structure-activity relationship study of tryptophan-based butyrylcholinesterase inhibitors.
Eur.J.Med.Chem., 208:112766-112766, 2020

PubMed Abstract: A series of tryptophan-based selective nanomolar butyrylcholinesterase (BChE) inhibitors was designed and synthesized. Compounds were optimized in terms of potency, selectivity, and synthetic accessibility. The crystal structure of the inhibitor 18 in complex with BChE revealed the molecular basis for its low nanomolar inhibition (IC = 2.8 nM). The favourable in vitro results enabled a first-in-animal in vivo efficacy and safety trial, which demonstrated a positive impact on fear-motivated and spatial long-term memory retrieval without any concomitant adverse motor effects. Altogether, this research culminated in a handful of new lead compounds with promising potential for symptomatic treatment of patients with Alzheimer's disease.

PubMed: 32919297
DOI: 10.1016/j.ejmech.2020.112766

実験手法

X-RAY DIFFRACTION (2.5 Å)