3EPX

Crystal structure of Trypanosoma vivax nucleoside hydrolase in complex with the inhibitor (2R,3R,4S)-2-(hydroxymethyl)-1-(quinolin-8-ylmethyl)pyrrolidin-3,4-diol

3EPX の概要

• エントリーDOI: 10.2210/pdb3epx/pdb
• 関連するPDBエントリー: 1HOZ 1HP0 1KIC 2FF2 3B9G 3EPW
• 分子名称: IAG-nucleoside hydrolase, CALCIUM ION, (2R,3R,4S)-2-(hydroxymethyl)-1-(quinolin-8-ylmethyl)pyrrolidine-3,4-diol, ... (5 entities in total)
• 機能のキーワード: rossmann fold, active site loops, aromatic stacking, hydrolase
• 由来する生物種: Trypanosoma vivax
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 75964.61

構造登録者

Versees, W.,Goeminne, A.,Berg, M.,Vandemeulebroucke, A.,Haemers, A.,Augustyns, K.,Steyaert, J. (登録日: 2008-09-30, 公開日: 2009-03-24, 最終更新日: 2024-10-16)

主引用文献

Versees, W.,Goeminne, A.,Berg, M.,Vandemeulebroucke, A.,Haemers, A.,Augustyns, K.,Steyaert, J.
Crystal structures of T. vivax nucleoside hydrolase in complex with new potent and specific inhibitors.
Biochim.Biophys.Acta, 1794:953-960, 2009

PubMed Abstract: Diseases caused by parasitic protozoa remain a major health problem, mainly due to old toxic drugs and rising drug resistance. Nucleoside hydrolases are key enzymes of the purine salvage pathway of parasites from the Trypanosomatidae family and are considered as possible drug targets. N-Arylmethyl substituted iminoribitols have been developed as selective nanomolar affinity inhibitors against the purine-specific nucleoside hydrolase of Trypanosoma vivax. The current paper describes the crystal structures of the T. vivax nucleoside hydrolase in complex with two of these inhibitors, to 1.3 and 1.85 A resolution. These high resolution structures provide an accurate picture of the mode of binding of these inhibitors and their mechanism of transition-state mimicry, and are valuable tools to guide further inhibitor design. Comparison of the current structures with previously solved structures of the enzyme in complex with ground-state and transition-state-analogue inhibitors also allows for the elucidation of a detailed molecular mechanism of active-site loop opening/closing. These loop movements can be coupled to the complex kinetic mechanism of the T. vivax nucleoside hydrolase.

PubMed: 19281874
DOI: 10.1016/j.bbapap.2009.02.011

実験手法

X-RAY DIFFRACTION (1.85 Å)