2W4X

BtGH84 in complex with STZ

2W4X の概要

• エントリーDOI: 10.2210/pdb2w4x/pdb
• 関連するPDBエントリー: 2CHN 2CHO 2J47 2J4G 2JIW 2VVN 2VVS 2VW3
• 分子名称: O-GLCNACASE BT_4395, GLYCEROL, Streptozotocin, ... (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
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 82713.50

構造登録者

He, Y.,Bubb, A.,Martinez-Fleites, C.,Davies, G.J. (登録日: 2008-12-02, 公開日: 2009-02-24, 最終更新日: 2023-12-13)

主引用文献

He, Y.,Martinez-Fleites, C.,Bubb, A.,Gloster, T.M.,Davies, G.J.
Structural Insight Into the Mechanism of Streptozotocin Inhibition of O-Glcnacase.
Carbohydr.Res., 344:627-, 2009

PubMed Abstract: Despite decades of its use in diabetes research, the mechanism of cytotoxicity of streptozotocin (STZ) toward pancreatic beta-islet cells has remained a topic of discussion. Although STZ toxicity is likely a function of its capacity to promote DNA alkylation, it has been proposed that STZ induces pancreatic beta-cell death through O-GlcNAcase inhibition. In this report, we explore the binding mode of STZ to a close homolog of human O-GlcNAcase, BtGH84 from Bacteroides thetaiotaomicron. Our results show that STZ binds in the enzyme active site in its intact form, without the formation of a covalent adduct, consistent with solution studies on BtGH84 and human O-GlcNAcase, as well as with structural work on a homolog from Clostridium perfringens. The active site of the BtGH84 is considerably deformed upon STZ binding and as a result the catalytic machinery is expelled from the binding cavity.

PubMed: 19217614
DOI: 10.1016/J.CARRES.2008.12.007

実験手法

X-RAY DIFFRACTION (2.42 Å)