随机门动力学调节了ubiquitination酶的催化活性
Manoj K Rout1, Curtis D Hodge, Craig J Markin
1Department of Biochemistry, University of Alberta , Edmonton, Alberta T6G 2H7, Canada.
Journal of the American Chemical Society
|November 26, 2014
概括
在Ubc13酶中,灵活的循环动态控制了DNA损伤和免疫反应所必需的催化活性. 这种静态门机制调节了Lys 63连接的聚比基链合成,这对于细胞信号传输至关重要.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 细胞信号传输 细胞信号传输
背景情况:
- DNA 损伤和先天性免疫反应依赖于 Lys 63 连接的多比基 (polyUb) 链.
- Ubc13是一种全素结合酶 (E2),通过其活性位点氨酸合成这些关键的多氨酸链.
研究的目的:
- 研究活性位点循环动态在Ubc13.的催化活性中的作用.
- 了解循环运动是如何调节 Lys 63 连接的多比基链的合成的.
主要方法:
- Ubc13活性位点循环残留物的位点定向突变发生.
- 酶动力学测试. 酶动力学测试.
- 核磁共振 (NMR) 的放松测量.
- 一个X射线晶体学.
- 分子动力学 (MD) 模拟.
- 在酵母体中的活体功能补充测试.
主要成果:
- 活点循环的快速pico-到nanosecond波动作为一个随机门,调节Ubc13的催化活性.
- 循环的精确平衡的开闭率对于酶功能至关重要.
- 影响循环动态的突变会在体内产生深刻的生物学后果.
结论:
- 活性位点循环动态对于Ubc13.的催化调节至关重要.
- 这种调节机制对于合成与lys 63结合的多比基链至关重要,影响DNA损伤和免疫反应.
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