6DHC

X-ray structure of BACE1 in complex with a bicyclic isoxazoline carboxamide as the P3 ligand

6DHC の概要

• エントリーDOI: 10.2210/pdb6dhc/pdb
• 分子名称: Beta-secretase 1, (3R,3aR,6aS)-N-[(4R,7S,8S,10R,13S)-8-hydroxy-10,17-dimethyl-7-(2-methylpropyl)-5,11,14-trioxo-13-(propan-2-yl)-2-thia-6,12,15-triazaoctadecan-4-yl]hexahydrofuro[3,2-d][1,2]oxazole-3-carboxamide, GLYCEROL, ... (6 entities in total)
• 機能のキーワード: bace1, memepsin 2, hydrolase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 149529.38

構造登録者

Mesecar, A.D.,Lendy, E.K. (登録日: 2018-05-19, 公開日: 2018-07-25, 最終更新日: 2024-10-23)

主引用文献

Ghosh, A.K.,Ghosh, K.,Brindisi, M.,Lendy, E.K.,Yen, Y.C.,Kumaragurubaran, N.,Huang, X.,Tang, J.,Mesecar, A.D.
Design, synthesis, X-ray studies, and biological evaluation of novel BACE1 inhibitors with bicyclic isoxazoline carboxamides as the P3 ligand.
Bioorg. Med. Chem. Lett., 28:2605-2610, 2018

PubMed Abstract: We describe the design, synthesis, X-ray studies, and biological evaluation of novel BACE1 inhibitors containing bicyclic isoxazoline carboxamides as the P3 ligand in combination with methyl cysteine, methylsulfonylalanine and Boc-amino alanine as P2 ligands. Inhibitor 3a displayed a BACE1 K value of 10.9 nM and EC of 343 nM. The X-ray structure of 3a bound to the active site of BACE1 was determined at 2.85 Å resolution. The structure revealed that the major molecular interactions between BACE1 and the bicyclic tetrahydrofuranyl isoxazoline heterocycle are van der Waals in nature.

PubMed: 29970308
DOI: 10.1016/j.bmcl.2018.06.045

実験手法

X-RAY DIFFRACTION (2.85 Å)