3DX3

Golgi alpha-Mannosidase II in complex with Mannostatin analog (1R,2R,3S,4R,5R)-5-aminocyclopentane-1,2,3,4-tetraol

3DX3 の概要

• エントリーDOI: 10.2210/pdb3dx3/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 3DX0 3DX1 3DX2 3DX4
• 分子名称: Alpha-mannosidase 2, 2-acetamido-2-deoxy-beta-D-glucopyranose, ZINC ION, ... (7 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: 120350.52

構造登録者

Kuntz, D.A.,Rose, D.R. (登録日: 2008-07-23, 公開日: 2009-07-07, 最終更新日: 2024-10-30)

主引用文献

Kuntz, D.A.,Zhong, W.,Guo, J.,Rose, D.R.,Boons, G.J.
The molecular basis of inhibition of Golgi alpha-mannosidase II by mannostatin A.
Chembiochem, 10:268-277, 2009

PubMed Abstract: Mannostatin A is a potent inhibitor of the mannose-trimming enzyme, Golgi alpha-mannosidase II (GMII), which acts late in the N-glycan processing pathway. Inhibition of this enzyme provides a route to blocking the transformation-associated changes in cancer cell surface oligosaccharide structures. Here, we report on the synthesis of new Mannostatin derivatives and analyze their binding in the active site of Drosophila GMII by X-ray crystallography. The results indicate that the interaction with the backbone carbonyl of Arg876 is crucial to the high potency of the inhibitor-an effect enhanced by the hydrophobic interaction between the thiomethyl group and an aromatic pocket vicinal to the cleavage site. The various structures indicate that differences in the hydration of protein-ligand complexes are also important determinants of plasticity as well as selectivity of inhibitor binding.

PubMed: 19101978
DOI: 10.1002/cbic.200800538

実験手法

X-RAY DIFFRACTION (1.42 Å)