在血基二氧化酶中逐步转移O原子:基板在环氧化物开放中的作用
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
概括
研究人员研究了基质的作用
科学领域:
- 生物化学
- 酵素学
- 有机化学
背景情况:
- 基于血的二氧化酶 (TDO) 是具有免疫抑制性质和生物医学相关性的金属蛋白.
- 了解TDO的催化机制对于开发向疗法至关重要.
研究的目的:
- 阐明基质的α-氨基基团在人类TDO催化过程中的氧原子转移中的特定作用.
- 研究基质修饰对TDO反应途径的影响.
主要方法:
- 用修改的α-氨基群 (碳或氧替代) 合成两个机械探针.
- 生物化学测定用于监测催化活性和产品形成.
- 广泛的光谱分析 (HPLC,UV-vis,HR-MS,NMR,IR) 用于表征反应中间体和产品.
主要成果:
- 在第一个氧原子转移后,基质修改显著改变了催化步骤.
- 鉴定出一种新型单氧化furoindoline产品,该产品来源于一个环氧英多尔中间体.
- 实验证据证实了基质的α-氨基组参与了环氧化物开放步骤.
结论:
- 这项研究表明,合成化合物可以调节TDO的阶段性氧原子转移机制.
- 提供了基质α-氨基基团在TDO中介反应中的催化作用的第一个实质证据.
- 进一步了解基于血的二氧化酶的机制.
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