在DEXH盒RNA基酶DHX9的晶体结构
Young Tae Lee1, E Allen Sickmier1, Simina Grigoriu1
1Accent Therapeutics, 1050 Waltham Street, Lexington, MA 02421, USA.
Acta crystallographica. Section D, Structural biology
|October 20, 2023
概括
哺乳动物DHX9 (DExH盒RNA基酶) 的晶体结构与其Drosophila正方体相比显示了保存的折叠和改变的RNA结合通道,为基酶状态和药物设计提供了洞察力.
科学领域:
- 生物化学 生化学
- 结构生物学 结构生物学
- 分子生物学分子生物学
背景情况:
- DHX9 (DExH-boxRNA基酶) 在基因表达和DNA复制中起着至关重要的作用.
- DHX9是瘤学中潜在的治疗点.
- 此前没有哺乳动物的DHX9结构可用.
研究的目的:
- 为了确定哺乳动物DHX9.9的晶体结构.
- 为了比较哺乳动物DHX9的结构与它的Drosophila Orthologue,MLE.
- 为了解DHX9功能和药物设计提供结构基础.
主要方法:
- 使用X射线晶体学来解决人类,狗和猫DHX9与ADP结合的结构.
- 在哺乳动物DHX9和Drosophila MLE之间进行了结构性比较.
主要成果:
- 在人类,狗和猫DHX9.9中观察到相同的结构折叠.
- 哺乳动物DHX9与Drosophila MLE共享保存的架构.
- 域定向和dsRNA结合域2 (dsRBD2) 占用率的差异改变了RNA结合通道,表明了不同的活性和非活性状态.
结论:
- 已确定的哺乳动物DHX9结构高度保存.
- 结构变异提供了对螺旋的动态状态的洞察.
- 这些结构是基于结构的药物设计的基础,在瘤学中向DHX9.
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