在细胞染色体P450中绘制基质识别路径
Navjeet Ahalawat1, Jagannath Mondal1
1Tata Institute of Fundamental Research, Center for Interdisciplinary Sciences , Hyderabad 500107 , India.
Journal of the American Chemical Society
|November 28, 2018
概括
细胞染色体P450酶使用单一的主导途径进入基质,涉及基质诱导的结构变化而不是大型蛋白质开口. 这说明了基质如何到达这些重要的金属酶的催化中心.
科学领域:
- 生物化学
- 酵素学
- 结构生物学
背景情况:
- 细胞染色体P450是药物代谢和解毒的关键金属酶.
- 基质进入其活性部位的机制尚不清楚,特别是考虑到封闭的晶体结构.
研究的目的:
- 调查P450的形状异质性是否导致基质获取途径变化.
- 阐明基质进入P450催化中心的机制.
主要方法:
- 原子分子动力学模拟 (多微秒).
- 对自发基质与P450cam相关性的分析.
- 马尔科夫状态建模和自由能量分析.
主要成果:
- 在P450cam中,基质的识别通过单一,明确的主导途径发生.
- 基板结合包括一个关键表面通道和基板诱导的侧链位移.
- 触媒中心的访问不需要大规模的蛋白质开放.
结论:
- 细胞染色体P450基质的识别是由基质诱导的结构重组驱动的.
- 建立了一个全面的基质访问模型,使以前的发现相协调.
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