与线性和循环性二核酸结合的G-四重复的溶液结构
Fernaldo Richtia Winnerdy1, Poulomi Das1, Brahim Heddi1,2
1School of Physical and Mathematical Sciences , Nanyang Technological University , Singapore 637371 , Singapore.
Journal of the American Chemical Society
|October 30, 2019
概括
关氨酸缺陷G-四重复体与含有关氨酸的二核酸结合,如循环GMP-AMP (cGAMP),具有微分子亲和力. 这种相互作用涉及二核酸
科学领域:
- 分子生物学
- 结构生物学
- 生物化学
背景情况:
- 循环二核酸是调节细胞过程的关键次要信使.
- 含有 (4n-1) 关氨酸的关氨酸缺陷G四复合体具有独特的结构性质.
- 之前的研究确立了这些关氨酸缺陷G四重复的形成.
研究的目的:
- 研究含瓜的二核酸与 (4n-1) G四重复结构的结合.
- 使用NMR光谱来阐明这种相互作用的结构基础.
- 为设计针对G四重复的特定联体提供见解.
主要方法:
- 用核磁共振 (NMR) 光谱来解决复合物的溶液结构.
- 研究了两种复合物:具有线性d ((AG) 的 (4n-1) G四重复合物和具有周期性cGAMP.
- 结构分析侧重于结合界面和结合相互作用.
主要成果:
- 发现A (4n-1) G四重复结构与含瓜的二核酸结合,具有微分子亲和力.
- 双核酸的关氨基基与G-四重复中空的G-三元体形成Hoogsteen键,完成一个G-四元体.
- 溶液结构显示出特定的结合相互作用,cGAMP对G三角形点具有强烈的结合.
结论:
- 关氨酸缺陷 (4n-1) G-四重复作为关氨酸含有的二核酸的结合部位.
- 观察到的结合机制为G-四重复的合理配体设计提供了基础.
- 其他含瓜的代谢物也可能结合G四重复,影响其功能和代谢物表达.
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