3EJS

Golgi alpha-Mannosidase II in complex with 5-substituted swainsonine analog: (5S)-5-[2'-(4-tert-butylphenyl)ethyl]-swainsonine

3EJS の概要

• エントリーDOI: 10.2210/pdb3ejs/pdb
• 関連するPDBエントリー: 1HTY 1HWW 1HXK 1PS2 1QWN 1R33 1R34 1TQV 2ALW 2F7O 2F7P 2F7Q 2F7R 2FYV 3BUB 3BUP 3CZN 3EJP 3EJQ 3EJR 3EJT 3EJU
• 分子名称: Alpha-mannosidase 2, 2-acetamido-2-deoxy-beta-D-glucopyranose, ZINC ION, ... (6 entities in total)
• 機能のキーワード: gh38 glycosidase, glycosidase, golgi apparatus, hydrolase, membrane, metal-binding, signal-anchor, transmembrane
• 由来する生物種: Drosophila melanogaster (Fruit fly)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 120439.87

構造登録者

Kuntz, D.A.,Shea, K.,Rose, D.R. (登録日: 2008-09-18, 公開日: 2009-10-13, 最終更新日: 2024-11-20)

主引用文献

Kuntz, D.A.,Nakayama, S.,Shea, K.,Hori, H.,Uto, Y.,Nagasawa, H.,Rose, D.R.
Structural Investigation of the Binding of 5-Substituted Swainsonine Analogues to Golgi alpha-Mannosidase II.
Chembiochem, 11:673-680, 2010

PubMed Abstract: Golgi alpha-mannosidase II (GMII) is a key enzyme in the N-glycosylation pathway and is a potential target for cancer chemotherapy. The natural product swainsonine is a potent inhibitor of GMII. In this paper we characterize the binding of 5alpha-substituted swainsonine analogues to the soluble catalytic domain of Drosophila GMII by X-ray crystallography. These inhibitors enjoy an advantage over previously reported GMII inhibitors in that they did not significantly decrease the inhibitory potential of the swainsonine head-group. The phenyl groups of these analogues occupy a portion of the binding site not previously seen to be populated with either substrate analogues or other inhibitors and they form novel hydrophobic interactions. They displace a well-organized water cluster, but the presence of a C(10) carbonyl allows the reestablishment of important hydrogen bonds. Already approximately tenfold more active against the Golgi enzyme than the lysosomal enzyme, these inhibitors offer the potential of being extended into the N-acetylglucosamine binding site of GMII for the creation of even more potent and selective GMII inhibitors.

PubMed: 20209559
DOI: 10.1002/cbic.200900750

実験手法

X-RAY DIFFRACTION (1.35 Å)