基质结合调节人体DNA原酶中的反氧信号
Elizabeth O'Brien1, Marilyn E Holt2, Lauren E Salay2
1Division of Chemistry and Chemical Engineering , California Institute of Technology , Pasadena , California 91125 , United States.
Journal of the American Chemical Society
|November 16, 2018
概括
在DNA复制过程中,DNA原酶使用 [4Fe4S] 集群进行信号传递. 它的氧化还原潜力在结合DNA和NTP时转移到生理范围,增强酶活性.
科学领域:
- 生物化学
- 分子生物学
- 酵素学
背景情况:
- DNA复制需要DNA原酶来合成RNA原蛋白.
- 酶是一种异构体 (p48/p58),具有不同的功能域.
- 在p58中的4Fe4S集群对酶活性至关重要.
研究的目的:
- 为了研究完整的DNA原酶异构体中的4Fe4S集群的氧化还原切换特性.
- 了解DNA和NTP结合如何影响集群的电化学信号.
- 探索氧化还原特性与原酶催化活性之间的关系.
主要方法:
- 用DNA电化学研究了完整的p48/p58原酶异构体.
- 进行了电化学测量以分析 [4Fe4S] 集群的氧化还原潜力.
- 进行了酶活性测定,以评估NTP结合对催化物的影响.
主要成果:
- [4Fe4S]集群的强有力的氧化还原信号需要同时结合DNA和NTP.
- NTP结合将集群的氧化还原潜力转移到生理范围 (约160mV与NHE).
- 用NTPs预加载原酶增强了催化活性,表明更活跃的构造.
结论:
- 基质结合 (DNA和NTP) 和形状变化调节了4Fe4S集群的氧化还原信号.
- 静电相互作用和子单元对齐影响集群的环境和信号.
- 这些发现对于理解具有 [4Fe4S] 集群的多子单元DNA处理酶中的信号具有重要意义.
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