3FKT

Crystal Structure of Human Beta Secretase Complexed with Spiropiperdine Iminohydantoin Inhibitor

「3E3W」から置き換えられました

3FKT の概要

• エントリーDOI: 10.2210/pdb3fkt/pdb
• 分子名称: Beta-secretase 1, N-(4-{[4-(cyclohexylamino)-1-(3-fluorophenyl)-2-oxo-1,3,8-triazaspiro[4.5]dec-3-en-8-yl]methyl}phenyl)acetamide (3 entities in total)
• 機能のキーワード: aspartyl protease, bace, alternative splicing, glycoprotein, hydrolase, membrane, polymorphism, protease, transmembrane, zymogen
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Membrane; Single-pass type I membrane protein: P56817
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 45614.35

構造登録者

Munshi, S. (登録日: 2008-12-17, 公開日: 2009-01-20, 最終更新日: 2024-10-30)

主引用文献

Barrow, J.C.,Stauffer, S.R.,Rittle, K.E.,Ngo, P.L.,Yang, M.S.,Graham, S.,McGaughey, G.,Holloway, K.,Tugusheva, S.K.,Lai, M.,Espeseth, A.S.,Xu, M.,Huang, Q.,Zuck, P.,Levorse, D.A.,Hazuda, D.,Vacca, J.P.
Discovery and X-ray Crystallographic Analysis of a Iminohydantoin Inhibitor of beta-Secretase
J.Med.Chem., 51:6259-6262, 2008

PubMed Abstract: A high-throughput screen at 100 microM inhibitor concentration for the BACE-1 enzyme revealed a novel spiropiperidine iminohydantoin aspartyl protease inhibitor template. An X-ray cocrystal structure with BACE-1 revealed a novel mode of binding whereby the inhibitor interacts with the catalytic aspartates via bridging water molecules. Using the crystal structure as a guide, potent compounds with good brain penetration were designed.

PubMed: 18811140
DOI: 10.1021/jm800914n

実験手法

X-RAY DIFFRACTION (1.9 Å)