一个 procaspase-7 zymogen 的晶体结构:激活和基质结合的机制
J Chai1, Q Wu, E Shiozaki
1Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ 08544, USA.
Cell
|November 10, 2001
概括
活跃的caspases通过非活跃的 procaspase zymogens 的蛋白质分离来执行亡. 结构分析揭示了 procaspase-7 激活和抑制剂结合如何诱导催化功能的结构变化.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 细胞亡是一个关键的细胞过程,由caspases执行.
- 卡斯帕斯被合成为需要激活的非活性细胞原体 (procaspases).
研究的目的:
- 阐明酶-7激活的结构机制.
- 了解抑制剂/基质与活性酶-7结合的结构基础.
主要方法:
- 使用X射线结晶学来确定procaspase-7和活性caspase-7的结构.
- 对齐摩根,活性和与抑制剂结合的形式进行比较结构分析.
主要成果:
- 普罗卡斯帕-7 呈现结构差异,排除了催化活性.
- 蛋白质分解裂变会诱导形状变化,使活性位形成.
- 抑制剂结合会诱导小子单元的显著形状变化 (180°翻转),稳定活性部位.
结论:
- 对酶-7的激活机制的结构见解.
- 证明抑制剂/基质与酶-7的结合是一种诱导适应过程.
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