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核糖体氧化酶在结构上是保存的,从 prokaryotes 到人类
Rasheduzzaman Chowdhury1, Rok Sekirnik1, Nigel C Brissett2
1The Department of Chemistry and Oxford Centre for Integrative Systems Biology, University of Oxford, Mansfield Road, Oxford OX1 3TA, U.K.
Nature
|May 13, 2014
概括
2-Oxoglutarate (2OG) 依赖的氧化酶,称为核糖体氧化酶 (ROXs),化核糖体蛋白质,影响翻译. 结构分析揭示了保存的折叠和新的二元化,定义了一个新的氧化酶子家族,并突出了进化灵活性.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 进化生物学 进化生物学
背景情况:
- 2-Oxoglutarate (2OG) -依赖的氧化酶通过脱甲基和化等修改来调节基因表达和蛋白质功能.
- 最近发现的核糖体氧酶 (ROXs) 对于翻译,细胞生长和分化至关重要,在各种生物体中发生.
- ROXs氧化特定的核糖体蛋白质,包括大肠杆菌中的氨酸和人类中的氨酸,这引发了关于它们的进化和结构关系的问题.
研究的目的:
- 调查核糖体氧化酶 (ROXs) 在原核生物和真核生物之间的结构和进化关系.
- 阐明ROXs的催化机制和基质特异性.
- 了解2OG-依赖氧化酶的演化及其多样化的功能.
主要方法:
- 来自大肠杆菌,R. marinus和人类的ROX晶体结构的比较结构分析 (MINA53,NO66).
- 生物化学测试以确认基酶活性和基质结合.
- 与其他含有JmjC域的基酶进行生物信息比较.
主要成果:
- ROX 分享高度保守的折叠,并表现出新的二元化模式,定义了一个新的2OG-依赖氧基酶的子家族.
- 结构数据证实ROXs作为基酶而不是脱甲基酶的功能,并揭示了适应用于基化不同的核糖体蛋白残留物.
- 进化性比较区分ROXs与其他JmjC域基酶,突出了铁结合基质氧化物种协调的灵活性,作为功能多样化的驱动力.
结论:
- 核糖体氧化酶 (ROXs) 是2OG依赖氧化酶的一个独特的亚家族,其结构保留,但基质特异性各异.
- ROXs的演变表明了协调化学的变化如何导致新的基化活动,扩大氧酶功能的剧目.
- 了解ROX的结构和功能提供了针对修改后的核糖体的潜在治疗策略.
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