4BEL

BACE2 XAPERONE COMPLEX

4BEL の概要

• エントリーDOI: 10.2210/pdb4bel/pdb
• 関連するPDBエントリー: 3ZKG 3ZKI 3ZKM 3ZKN 3ZKQ 3ZKS 3ZKX 3ZL7 3ZOV 4BFB
• 分子名称: BETA-SECRETASE 2, XA4813, CHLORIDE ION, ... (5 entities in total)
• 機能のキーワード: hydrolase-immune system complex, nanobody, hydrolase/immune system
• 由来する生物種: HOMO SAPIENS (HUMAN); 詳細
• 細胞内の位置: Membrane; Single-pass type I membrane protein: Q9Y5Z0
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 111115.94

構造登録者

Banner, D.W.,Kuglstatter, A.,Benz, J.,Stihle, M.,Ruf, A. (登録日: 2013-03-11, 公開日: 2013-05-29, 最終更新日: 2024-10-16)

主引用文献

Banner, D.W.,Gsell, B.,Benz, J.,Bertschinger, J.,Burger, D.,Brack, S.,Cuppuleri, S.,Debulpaep, M.,Gast, A.,Grabulovski, D.,Hennig, M.,Hilpert, H.,Huber, W.,Kuglstatter, A.,Kusznir, E.,Laeremans, T.,Matile, H.,Miscenic, C.,Rufer, A.,Schlatter, D.,Steyeart, J.,Stihle, M.,Thoma, R.,Weber, M.,Ruf, A.
Mapping the Conformational Space Accessible to Bace2 Using Surface Mutants and Co-Crystals with Fab-Fragments, Fynomers, and Xaperones
Acta Crystallogr.,Sect.D, 69:1124-, 2013

PubMed Abstract: The aspartic protease BACE2 is responsible for the shedding of the transmembrane protein Tmem27 from the surface of pancreatic β-cells, which leads to inactivation of the β-cell proliferating activity of Tmem27. This role of BACE2 in the control of β-cell maintenance suggests BACE2 as a drug target for diabetes. Inhibition of BACE2 has recently been shown to lead to improved control of glucose homeostasis and to increased insulin levels in insulin-resistant mice. BACE2 has 52% sequence identity to the well studied Alzheimer's disease target enzyme β-secretase (BACE1). High-resolution BACE2 structures would contribute significantly to the investigation of this enzyme as either a drug target or anti-target. Surface mutagenesis, BACE2-binding antibody Fab fragments, single-domain camelid antibody VHH fragments (Xaperones) and Fyn-kinase-derived SH3 domains (Fynomers) were used as crystallization helpers to obtain the first high-resolution structures of BACE2. Eight crystal structures in six different packing environments define an ensemble of low-energy conformations available to the enzyme. Here, the different strategies used for raising and selecting BACE2 binders for cocrystallization are described and the crystallization success, crystal quality and the time and resources needed to obtain suitable crystals are compared.

PubMed: 23695257
DOI: 10.1107/S0907444913006574

実験手法

X-RAY DIFFRACTION (1.85 Å)