蛋白质酸化和分子间电子转移:对激素生物合成途径的联合实验和计算研究
Andy Zöllner1, Melissa A Pasquinelli, Rita Bernhardt
1Universität des Saarlandes, 66123 Saarbrücken, Germany.
Journal of the American Chemical Society
|March 16, 2007
概括
在上腺素 (Adx) 中Thr-71的蛋白质酸化增强了电子转移到细胞染色体P450 (CYP11A1). 这种修改产生了二次结合复合体,提高了生物电子转移效率.
科学领域:
- 生物化学 生物化学
- 生物物理学的生物物理.
- 酶学 是一种酶学.
背景情况:
- 蛋白质酸化是一种关键的翻译后修饰,调节酶活性.
- 酸化对分子间电子转移动学的影响仍未得到充分研究.
- 生物电子转移对于各种细胞过程至关重要.
研究的目的:
- 研究上腺素 (Adx) 在Thr-71酸化在调节电子转移反应中的作用.
- 评估酸化如何影响Adx,上腺素减少酶 (AdR) 和细胞染色体P450 (CYP11A1) 之间的相互作用.
主要方法:
- 利用光学生物传感器实验来测量结合亲和力.
- 采用Adx度依赖的停止流体实验来描述电子转移动力学.
- 进行布朗动力学 (BD) 模拟,以建模蛋白相互作用和电子转移途径.
主要成果:
- 在Thr-71中Adx的酸化稍微增加了与CYP11A1ox的结合亲和力,但不是AdRox.
- 化Adx-CYP11A1反应的电子转移动力学显示了加速.
- 两相反应动力学仅与化Adx一起观察到,这表明二次结合复合体.
结论:
- 在Thr-71中Adx通过素激酶2 (CK2) 的酸化会影响其与CYP11A1.1的相互作用.
- 这种酸化通过促进具有改进合的二次结合复合体来提高电子转移效率.
- 这些发现突出了生物学电子转移系统中翻译后修饰的调节作用.
相关概念视频
Protein Kinases and Phosphatases
Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Protein Kinases and Phosphatases
Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Phosphorylation
The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
Phosphorylation
The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
Secondary Messengers in Hormone Action
Water-soluble hormones cannot cross the plasma membrane, so they rely on protein receptors that span the membrane to trigger intracellular signaling pathways. These pathways then activate second messengers inside the cell, including cAMP or calcium ions.
Many hormones bind to transmembrane G protein-coupled receptors that connect to regulatory G proteins. These G proteins can then activate enzymes such as adenylyl cyclase or phospholipase C. Adenylyl cyclase converts ATP to cAMP, activating...
Many hormones bind to transmembrane G protein-coupled receptors that connect to regulatory G proteins. These G proteins can then activate enzymes such as adenylyl cyclase or phospholipase C. Adenylyl cyclase converts ATP to cAMP, activating...
Interactions Between Signaling Pathways
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...


