ヘムベースのトリプトファン二酸化酵素における段階的なO原子移転:エポキシードリング開封における基板アンモニアの役割

Inchul Shin¹, Brett R Ambler², Daniel Wherritt¹

¹Department of Chemistry , University of Texas at San Antonio , San Antonio , Texas 78249 , United States.

Journal of the American Chemical Society

|March 7, 2018

まとめ

研究者は,基板の役割を調査した.

科学分野:

生物化学
酵素学
有機化学

背景:

ヘム基のトリプトファンダイオキシゲナーゼ (TDO) は,免疫抑制特性を有する金属タンパク質であり,生物医学的に重要である.
TDOの触媒メカニズムを理解することは,標的治療の開発に不可欠です.

研究の目的:

人間のTDO触媒の酸素原子移転における基質のα-アミノ群の特定の役割を解明する.
TDO反応経路に対する基質改変の影響を調査する.

主な方法:

改変されたα-アミノ群 (炭素または酸素置換) を含む2つの機械的探査機の合成.
触媒活動と産物形成を監視する生化学的測定法
広範囲のスペクトル解析 (HPLC,UV-vis,HR-MS,NMR,IR) で,反応中間物質と産物を特徴づけている.

主要な成果:

基板の改変は,最初の酸素原子移転後に触媒段階を大幅に変化させた.
エポキシインドール中間産物から生まれた新しいモノオキシインドール製品が特定されました.
実験的証拠は,亜基体のα-アミノ群がエポキシードリング開き段階に関与することを確認した.

結論:

この研究は,合成化合物がTDOの段階的な酸素原子移転機構を調節できることを示しています.
TDO媒介反応における基質のα-アミノ群の触媒作用に関する最初の実質的な証拠を提供する.
ヘム基のトリプトファン・ダイオキシゲナーズのメカニズムを理解する.

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