设计和应用的基本氨基酸显示增强的疏水性
Juliana K Kretsinger1, Joel P Schneider
1Department of Chemistry and Biochemistry, University of Delaware, Newark, DE 19716-2522, USA.
Journal of the American Chemical Society
|June 26, 2003
概括
有甲基的新型非编码氨基酸增强了蛋白质的稳定性和折叠性. 单甲基二氨基酸 (mmdap) 稳定了蛋白质异构体,而三甲基二氨基酸 (tmdap) 则使它们不稳定. 甲基二胺烯酸 (dmdap) 意外地形成了稳定的同类三元体.
科学领域:
- 蛋白质设计与工程 蛋白质设计与工程
- 生物化学 生物化学
- 结构生物学 结构生物学
背景情况:
- 蛋白质的设计需要新的氨基酸残留物来控制蛋白质的结构和功能.
- 氨基酸 (dap) 是一种基本的氨基酸,可以经过化学修饰.
- 了解修改如何影响蛋白质折叠对于蛋白质工程至关重要.
研究的目的:
- 为了合成和表征新的非编码氨基酸:单,二,三甲基二氨基酸 (mmdap,dmdap,tmdap).
- 评估这些改性残留物在蛋白质设计中的实用性,特别是促进内部盐桥形成.
- 评估这些残留物对GCN4-p1卷轴系统的稳定性和折叠偏好的影响.
主要方法:
- 合成MMDAP,DMDAP和TMDAP残留物.
- 将这些残留物纳入GCN4-p1体在位置16.
- 使用生物物理技术研究修饰的GCN4-p1和含有酸的之间的异构化.
- 对类同型三聚化和热展开的分析.
主要成果:
- 与含有mdap的异构体相比,含有mdap的异构体的稳定性增加了0.5kcal/mol. 与dap衍生的异构体相比,异构体的稳定性增加了0.5kcal/mol.
- 含有TMDAP的异构体显著不稳定,这表明干阻碍.
- Dmdap意外诱导了的同位三分化,形成了一个稳定的三分体 (ΔG = 11.8 kcal/mol).
结论:
- 甲基化二氨基酸衍生物为蛋白质设计提供可调节的特性.
- 氨基酸大小和疏水性的小变化可以显著改变蛋白质折叠偏好.
- 这些新型残留物为蛋白质化学家提供了新的工具,以设计蛋白质结构和稳定性.
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