3FZ0

Inosine-Guanosine Nucleoside Hydrolase (IG-NH)

3FZ0 の概要

• エントリーDOI: 10.2210/pdb3fz0/pdb
• 関連するPDBエントリー: 1KIC 1Q8F 2MAS 3B9X
• 分子名称: Nucleoside hydrolase, putative, CALCIUM ION, 2-[BIS-(2-HYDROXY-ETHYL)-AMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL, ... (4 entities in total)
• 機能のキーワード: nh fold, open alpha/beta structure, glycosidase, hydrolase
• 由来する生物種: Trypanosoma brucei
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 159736.57

構造登録者

Vandemeulebroucke, A.,Minici, C.,Bruno, I.,Muzzolini, L.,Tornaghi, P.,Parkin, D.W.,Schramm, V.L.,Versees, W.,Steyaert, J.,Degano, M. (登録日: 2009-01-23, 公開日: 2010-01-26, 最終更新日: 2023-11-01)

主引用文献

Vandemeulebroucke, A.,Minici, C.,Bruno, I.,Muzzolini, L.,Tornaghi, P.,Parkin, D.W.,Versees, W.,Steyaert, J.,Degano, M.
Structure and mechanism of the 6-oxopurine nucleosidase from Trypanosoma brucei brucei
Biochemistry, 49:8999-9010, 2010

PubMed Abstract: Trypanosomes are purine-auxotrophic parasites that depend upon nucleoside hydrolase (NH) activity to salvage nitrogenous bases necessary for nucleic acid and cofactor synthesis. Nonspecific and purine-specific NHs have been widely studied, yet little is known about the 6-oxopurine-specific isozymes, although they are thought to play a primary role in the catabolism of exogenously derived nucleosides. Here, we report the first functional and structural characterization of the inosine-guanosine-specific NH from Trypanosoma brucei brucei. The enzyme shows near diffusion-limited efficiency coupled with a clear specificity for 6-oxopurine nucleosides achieved through a catalytic selection of these substrates. Pre-steady-state kinetic analysis reveals ordered product release, and a rate-limiting structural rearrangement that is associated with the release of the product, ribose. The crystal structure of this trypanosomal NH determined to 2.5 Å resolution reveals distinctive features compared to those of both purine- and pyrimidine-specific isozymes in the framework of the conserved and versatile NH fold. Nanomolar iminoribitol-based inhibitors identified in this study represent important lead compounds for the development of novel therapeutic strategies against trypanosomal diseases.

PubMed: 20825170
DOI: 10.1021/bi100697d

実験手法

X-RAY DIFFRACTION (2.5 Å)