3DUY

Crystal structure of human beta-secretase in complex with NVP-AFJ144

3DUY の概要

• エントリーDOI: 10.2210/pdb3duy/pdb
• 関連するPDBエントリー: 3DV1 3DV5
• 分子名称: Beta-secretase 1, (2R,4S,5S)-N-butyl-4-hydroxy-2,7-dimethyl-5-{[N-(4-methylpentanoyl)-L-methionyl]amino}octanamide (3 entities in total)
• 機能のキーワード: beta-secretase, bace1, memapsin2, enzyme inhibitor complex, alzheimer's disease, alternative splicing, aspartyl protease, glycoprotein, hydrolase, membrane, protease, transmembrane, zymogen
• 由来する生物種: Homo sapiens
• 細胞内の位置: Membrane; Single-pass type I membrane protein: P56817
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 135795.23

構造登録者

Rondeau, J.-M. (登録日: 2008-07-18, 公開日: 2009-02-24, 最終更新日: 2024-11-06)

主引用文献

Machauer, R.,Veenstra, S.,Rondeau, J.M.,Tintelnot-Blomley, M.,Betschart, C.,Neumann, U.,Paganetti, P.
Structure-based design and synthesis of macrocyclic peptidomimetic beta-secretase (BACE-1) inhibitors.
Bioorg.Med.Chem.Lett., 19:1361-1365, 2009

PubMed Abstract: The hydroxyethylene octapeptide inhibitor OM99-2 served as starting point to create the tripeptide inhibitor 1 and its analogues 2a and b. An X-ray co-crystal structure of 1 with BACE-1 allowed the design and syntheses of a series of macrocyclic analogues 3a-h covalently linking the P1 and P3 side-chains. These inhibitors show improved enzymatic potency over their open-chain analogue. Inhibitor 3h also shows activity in a cellular system.

PubMed: 19195886
DOI: 10.1016/j.bmcl.2009.01.036

実験手法

X-RAY DIFFRACTION (1.97 Å)