2XJ7

BtGH84 in complex with 6-acetamido-6-deoxy-castanospermine

2XJ7 の概要

• エントリーDOI: 10.2210/pdb2xj7/pdb
• 関連するPDBエントリー: 2CHN 2CHO 2J47 2J4G 2JIW 2VVN 2VVS 2W4X 2W66 2W67 2WCA 2WZH 2WZI 2X0H
• 分子名称: O-GLCNACASE BT_4395, 6-ACETAMIDO-6-DEOXY-CASTANOSPERMINE, CALCIUM ION, ... (4 entities in total)
• 機能のキーワード: hydrolase, inhibitor
• 由来する生物種: BACTEROIDES THETAIOTAOMICRON VPI-5482
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 165172.90

構造登録者

He, Y.,Davies, G.J. (登録日: 2010-07-02, 公開日: 2010-09-29, 最終更新日: 2023-12-20)

主引用文献

Macauley, M.S.,He, Y.,Gloster, T.M.,Stubbs, K.A.,Davies, G.J.,Vocadlo, D.J.
Inhibition of O-Glcnacase Using a Potent and Cell-Permeable Inhibitor Does not Induce Insulin Resistance in 3T3-L1 Adipocytes.
Chem.Biol., 17:937-, 2010

PubMed Abstract: To probe increased O-GlcNAc levels as an independent mechanism governing insulin resistance in 3T3-L1 adipocytes, a new class of O-GlcNAcase (OGA) inhibitor was studied. 6-Acetamido-6-deoxy-castanospermine (6-Ac-Cas) is a potent inhibitor of OGA. The structure of 6-Ac-Cas bound in the active site of an OGA homolog reveals structural features contributing to its potency. Treatment of 3T3-L1 adipocytes with 6-Ac-Cas increases O-GlcNAc levels in a dose-dependent manner. These increases in O-GlcNAc levels do not induce insulin resistance functionally, measured using a 2-deoxyglucose (2-DOG) uptake assay, or at the molecular level, determined by evaluating levels of phosphorylated IRS-1 and Akt. These results, and others described, provide a structural blueprint for improved inhibitors and collectively suggest that increased O-GlcNAc levels, brought about by inhibition of OGA, does not by itself cause insulin resistance in 3T3-L1 adipocytes.

PubMed: 20851343
DOI: 10.1016/J.CHEMBIOL.2010.07.006

実験手法

X-RAY DIFFRACTION (2 Å)