2ZHU

Crystal structure of BACE1 at pH 5.0

2ZHU の概要

• エントリーDOI: 10.2210/pdb2zhu/pdb
• 関連するPDBエントリー: 2ZHR 2ZHS 2ZHT 2ZHV
• 分子名称: Beta-secretase 1 (2 entities in total)
• 機能のキーワード: ph 5.0, alternative splicing, aspartyl protease, glycoprotein, hydrolase, membrane, 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: 45900.50

構造登録者

Shimizu, H.,Nukina, N. (登録日: 2008-02-08, 公開日: 2008-04-22, 最終更新日: 2024-10-30)

主引用文献

Shimizu, H.,Tosaki, A.,Kaneko, K.,Hisano, T.,Sakurai, T.,Nukina, N.
Crystal structure of an active form of BACE1, an enzyme responsible for amyloid beta protein production
Mol.Cell.Biol., 28:3663-3671, 2008

PubMed Abstract: BACE1 (beta-secretase) is a transmembrane aspartic protease that cleaves the beta-amyloid precursor protein and generates the amyloid beta peptide (Abeta). BACE1 cycles between the cell surface and the endosomal system many times and becomes activated interconvertibly during its cellular trafficking, leading to the production of Abeta. Here we report the crystal structure of the catalytically active form of BACE1. The active form has novel structural features involving the conformation of the flap and subsites that promote substrate binding. The functionally essential residues and water molecules are well defined and play a key role in the iterative activation of BACE1. We further describe the crystal structure of the dehydrated form of BACE1, showing that BACE1 activity is dependent on the dynamics of a catalytically required Asp-bound water molecule, which directly affects its catalytic properties. These findings provide insight into a novel regulation of BACE1 activity and elucidate how BACE1 modulates its activity during cellular trafficking.

PubMed: 18378702
DOI: 10.1128/MCB.02185-07

実験手法

X-RAY DIFFRACTION (2.4 Å)