通过ATP结合和水解转化MutL:DNA不匹配修复中的一个开关
1Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Cell
|April 13, 1999
概括
细菌的MutL蛋白,一种参与DNA修复的ATPase,形成二极体来解ATP. DNA结合刺激了这个过程,这表明它在协调DNA不匹配修复中的作用.
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:
- MutL蛋白对于DNA不匹配的修复至关重要,并且具有ATPase活性.
- MutL属于ATPase超级家族,其中包括DNA拓酶II和Hsp90.0.
研究的目的:
- 为了阐明大肠杆菌MutL的ATPase活性的结构基础.
- 了解ATP水解的机制及其通过DNA的调节.
主要方法:
- 使用X射线晶体学来确定与ADPNP和ADP结合的大肠杆菌MutL ATPase片段 (LN40) 的结构.
- 分析核酸结合和水解后的结构变化.
主要成果:
- 晶体结构揭示了核酸结合后的有序残留物,促进了ADPNP结合和LN40二元化.
- ATP水解触发了关键环的释放和LN40二元体的解离.
- 对于ATP水解来说,LN40的二元化是必不可少的,并且是限制速率的.
结论:
- MutL二元化是其ATPase循环中的关键步骤.
- MutL的ATPase活动的DNA刺激表明,DNA不匹配修复协调的调节开关机制.
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In order to be passed through generations, genomic DNA must be undamaged and error-free. However, every day, DNA in a cell undergoes several thousand to a million damaging events by natural causes and external factors. Ionizing radiation such as UV rays, free radicals produced during cellular respiration, and hydrolytic damage from metabolic reactions can alter the structure of DNA. Damages caused include single-base alteration, base dimerization, chain breaks, and cross-linkage.
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In order to be passed through generations, genomic DNA must be undamaged and error-free. However, every day, DNA in a cell undergoes several thousand to a million damaging events by natural causes and external factors. Ionizing radiation such as UV rays, free radicals produced during cellular respiration, and hydrolytic damage from metabolic reactions can alter the structure of DNA. Damages caused include single-base alteration, base dimerization, chain breaks, and cross-linkage.
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