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门DNA识别和IIA型拓聚合酶曲的结构基础
1Chemical Biology Graduate Program, Department of Chemistry, College of Chemistry, University of California, Berkeley, California 94720-3220, USA.
Nature
|December 22, 2007
概括
研究人员可视化了酵母Topoisomerase II (Topo II) 如何结合DNA,揭示了类似于DNA重塑蛋白的机制. 这种结构洞察力澄清了DNA处理,并表明了不同类型的拓酶之间的进化联系.
科学领域:
- 生物化学 生化学
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 二型拓酶对DNA管理至关重要,是关键的治疗点.
- 对这些酶如何结合DNA的详细分子理解是有限的.
研究的目的:
- 为了阐明由Saccharomyces cerevisiae的II型多波色酶结合DNA的结构基础.
- 了解DNA曲和催化部位形成的机制.
主要方法:
- 采用X射线晶体学,确定了酵母Topo II与DNA复合的DNA结合和分裂核心的结构.
- 结构分析的重点是酶-DNA相互作用和形状变化.
主要成果:
- 结构显示Topo II诱导DNA显著的150度曲,采用类似于DNA重塑蛋白质的机制.
- DNA 结合引发了大量的蛋白质构造变化,形成了一个带有反应性氨酸和离子的双部分催化部位.
- 催化部位的结构类似于IA型的拓酶,这表明了进化联系.
结论:
- 这项研究提供了Topo II-DNA结合的第一个分子视图,解释了DNA曲和催化位形成.
- 这些发现支持了不同类型的拓酶家族之间的进化关系.
- 结合DNA促进了酶二分化接口的开放,这是酶作用期间DNA传输的关键步骤.
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