相关实验视频
Updated: Jun 23, 2026
11:13
Identification of Kinase-substrate Pairs Using High Throughput Screening
Published on: August 29, 2015
经典的人类蛋白质氨酸酸组的大规模结构分析
Alastair J Barr1, Emilie Ugochukwu, Wen Hwa Lee
1University of Oxford, Structural Genomics Consortium, Old Road Campus Research Building, Roosevelt Drive, Headington, Oxford, OX3 7DQ, UK. alastair.barr@sgc.ox.ac.uk
Cell
|January 27, 2009
概括
这项研究揭示了蛋白质氨酸酸酶 (PTP) 家族内的多样性结构和功能. 它确定了催化惰性PTP,并提出了PTP调节和基质结合的新模型.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 分子生物学分子生物学
背景情况:
- 蛋白氨酸酸酶 (PTPs) 是通过脱酸化调节细胞过程的关键酶.
- 了解PTP多样性是解读复杂细胞信号通路的关键.
研究的目的:
- 用结构和功能数据全面分析古典人类PTP家族.
- 调查PTP多样性,催化活性,基质识别和监管机制.
主要方法:
- 分析了22个新的和现有的人类PTP晶体结构.
- 结构比较以确定保存和多样化的特征.
- 酶分析测试以确定催化活性.
- 模拟PTP二分化和调节的模型.
主要成果:
- 人类PTP表现出各种各样的表面特性,尽管保留了折叠.
- 经常观察到二次基质结合口袋,影响基质识别和抑制剂设计.
- 确定了四种不同的催化循环 (WPD) 形状,表明有一个循环关闭机制.
- 确定了PTPD1,PTPD2和HDPTP是催化无效的.
- 为RPTPgamma/zeta提出了一个新的"头到脚"二分化模型,与"抑制"模型不同.
结论:
- PTP家族在结构,活动和调节方面表现出显著的家族内部多样性.
- 结构洞察力有助于理解基质结合和选择性抑制剂的发展.
- 对于PTP自我调节的新模型为抑制机制提供了分子基础.
相关概念视频
01:02Phosphorylation
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...
02:54Protein 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...
02:26Protein Networks
An organism can have thousands of different proteins, and these proteins must cooperate to ensure the health of an organism. Proteins bind to other proteins and form complexes to carry out their functions. Many proteins interact with multiple other proteins creating a complex network of protein interactions.
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
02:54Protein 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...