2W67

BtGH84 in complex with FMA34

2W67 の概要

• エントリーDOI: 10.2210/pdb2w67/pdb
• 関連するPDBエントリー: 2CHN 2CHO 2J47 2J4G 2JIW 2VVN 2VVS 2VW3 2W4X 2W66
• 分子名称: O-GLCNACASE BT_4395, N-[(3S,4R,5R,6R)-4,5,6-trihydroxyazepan-3-yl]acetamide, GLYCEROL, ... (5 entities in total)
• 機能のキーワード: glycoside hydrolase, complex, hydrolase, inhibitor, glycosidase
• 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: 165212.92

構造登録者

He, Y.,Davies, G.J. (登録日: 2008-12-17, 公開日: 2009-04-14, 最終更新日: 2023-12-13)

主引用文献

Marcelo, F.,He, Y.,Yuzwa, S.A.,Nieto, L.,Jimenez-Barbero, J.,Sollogoub, M.,Vocadlo, D.J.,Davies, G.J.,Bleriot, Y.
Molecular Basis for Inhibition of Gh84 Glycoside Hydrolases by Substituted Azepanes: Conformational Flexibility Enables Probing of Substrate Distortion.
J.Am.Chem.Soc., 131:5390-, 2009

PubMed Abstract: Here we report the synthesis of a series of polyhydroxylated 3- and 5-acetamido azepanes and detail the molecular basis of their inhibition of family 84 glycoside hydrolases. These family 84 enzymes include human O-GlcNAcase, an enzyme involved in post-translational processing of intracellular proteins modified by O-linked beta-N-acetylglucosamine residues. Detailed structural analysis of the binding of these azepanes to BtGH84, a bacterial homologue of O-GlcNAcase, highlights their conformational flexibility. Molecular mechanics and molecular dynamics calculations reveal that binding to the enzyme involves significant conformational distortion of these inhibitors from their preferred solution conformations. The binding of these azepanes provides structural insight into substrate distortion that likely occurs along the reaction coordinate followed by O-GlcNAcase during glycoside hydrolysis. This class of inhibitors may prove to be useful probes for evaluating the conformational itineraries of glycosidases and aid the development of more potent and specific glycosidase inhibitors.

PubMed: 19331390
DOI: 10.1021/JA809776R

実験手法

X-RAY DIFFRACTION (2.25 Å)