不同类型的氨基酸残留物在球状蛋白质中的温度依赖的动态转换
Yinglong Miao1, Zheng Yi, Dennis C Glass
1University of Tennessee/Oak Ridge National Laboratory Center for Molecular Biophysics, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831, United States.
Journal of the American Chemical Society
|November 13, 2012
概括
研究蛋白质动力学揭示了温度如何影响氨基酸残留的运动. 疏水性残留物首先会变得活跃,随着温度的升高,水友性残留物也会变得活跃.
科学领域:
- 生物物理学的生物物理.
- 计算生物学 计算生物学
- 蛋白质动力学 蛋白质动力学
背景情况:
- 细胞染色体P450cam是一种关键的酶,参与药物代谢和解毒.
- 了解蛋白质动态对于阐明酶功能和机制至关重要.
- 氨基酸残留的动态在蛋白质的灵活性和活性中起着至关重要的作用.
研究的目的:
- 为了研究不同类型的氨基酸残留在细胞染色体P450cam.cam.的温度依赖的纳秒动态.
- 阐明温度诱导的形状变化期间疏水,芳香和水性残留物之间的相互作用.
- 为了将残留动态与结和水合水相互作用相关联.
主要方法:
- 进行了弹性不连贯中子散射 (EINS) 实验,以探测原子运动.
- 用分子动力学 (MD) 模拟来模拟原子水平上的蛋白质行为.
- 结合EINS和MD方法提供了对蛋白质动态的互补见解.
主要成果:
- 在100-160K之间,疏水和芳香残留中的无调运动被激活.
- 在较低的温度下,由于结合,性残留物运动被抑制.
- 在180-220K时,水友侧链的水激活跳跃变得明显,加上键放松.
结论:
- 蛋白质动态取决于温度,对不同类型的残留物有不同的行为.
- 在较低的温度下,细胞染色体P450cam的疏水性核心"醒来",然后在较高的温度下,水友表面"醒来".
- 化水和键显著影响氨基酸残留的温度依赖的动态.
相关概念视频
Protein Denaturation
The function of proteins depends on their native three-dimensional structure, which is dictated by the amino acid sequence of the specific protein. Folding of the polypeptide chain takes place under specific conditions that energetically favor the folded conformation. In contrast, protein denaturation occurs spontaneously under unfavorable conditions that disrupt the integrity of the folded conformation. Thus, the chemical and physical environment of a protein, such as significant changes in pH...
Phase Transitions: Melting and Freezing
Heating a crystalline solid increases the average energy of its atoms, molecules, or ions, and the solid gets hotter. At some point, the added energy becomes large enough to partially overcome the forces holding the molecules or ions of the solid in their fixed positions, and the solid begins the process of transitioning to the liquid state or melting. At this point, the temperature of the solid stops rising, despite the continual input of heat, and it remains constant until all of the solid is...
Protein Folding
Overview
Protein Folding
Proteins are chains of amino acids linked together by peptide bonds. Upon synthesis, a protein folds into a three-dimensional conformation, critical to its biological function. Interactions between its constituent amino acids guide protein folding, and hence the protein structure is primarily dependent on its amino acid sequence.
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
Cooperative Allosteric Transitions
Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
Cooperative Allosteric Transitions
Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...


