作为核受体-协同激活器相互作用的调节器,烯螺旋长度作为核受体-协同激活器相互作用的调节器
Sascha Fuchs1, Hoang D Nguyen, Trang T P Phan
1Laboratory of Chemical Biology, Department of Biomedical Engineering, Technische Universiteit Eindhoven, Den Dolech 2, 5612 AZ Eindhoven, The Netherlands.
Journal of the American Chemical Society
|February 27, 2013
概括
研究人员发现了一种新的PXLXXLLXXP核受体结合共识,扩大了对典型LXXLL动机的理解. 这一发现为设计针对基因转录调节的药物提供了新的结构性见解.
科学领域:
- 分子生物学分子生物学
- 结构生物学 结构生物学
- 药物发现 药物发现 药物发现
背景情况:
- 核受体联合激活剂结合对于基因转录至关重要.
- 已知保存的LXXLL图案调解了这种相互作用.
- 了解超出LXXLL的序列特异性对于药物开发至关重要.
研究的目的:
- 为了确定核受体的新识别动机.
- 为了研究侧面残留在协活性剂结合中的作用.
- 为核受体-协同激活剂相互作用提供结构性见解.
主要方法:
- 核糖体显示被用来选新的结合基因.
- 分子建模被用来分析结构相互作用.
- 射线晶体学提供了高分辨率的结构数据.
主要成果:
- 一个新的,高度进化的PXLXXLLXXP约束性共识被发现.
- 这项研究阐明了侧翼林在α-螺旋形成和受体相互作用中的作用.
- 确定了调节受体-协同激活剂相互作用的新结构参数.
结论:
- PXLXXLLXXP图案代表了已知的核受体结合序列的显著扩展.
- 结构洞察力揭示了侧面残留物如何优化与受体的α-螺旋相互作用.
- 这些发现有助于设计用于核受体介导基因调节的向抑制剂.
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