林异构酶的隐藏替代结构对于催化是必不可少的
James S Fraser1, Michael W Clarkson, Sheena C Degnan
1Department of Molecular and Cell Biology/QB3, University of California, Berkeley, California 94720-3220, USA.
Nature
|December 4, 2009
概括
理解酶催化需要对蛋白质动态的原子层次洞察. 这项研究揭示了人类环素A (PPIA) 中的集体运动如何通过稳定功能性小形状来直接促进其催化能力.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 酶学 是一种酶学.
背景情况:
- 酶催化与蛋白质动力学密切相关,但理解罕见的构造子状态的原子层机制仍然是一个挑战.
- 像X射线结晶学和NMR光谱学这样的现有方法提供了对酶动态和催化状态的补充但不完整的观点.
研究的目的:
- 在原子层面上对人类烯异构酶,环素A (PPIA) 的相互转换子状态进行结构性表征.
- 通过将形态动态与催化速率联系起来,阐明集体蛋白质运动在酶催化中的作用.
主要方法:
- 环境温度X射线晶体数据收集与自动电子密度采样相结合,以解决罕见的蛋白质构造.
- 局部导向的突变发生,以稳定先前隐藏的环素A的小构造.
- 进行NMR放松研究,以分析溶液中的酶动态.
主要成果:
- 双结晶学策略成功地揭开了环林A (PPIA) 的相互转换子状态.
- 在活性位点以外的保守突变逆转了子状态之间的平衡,并稳定了小形状.
- 这种突变显著降低了构造性相互转换率和催化率,证明了直接联系.
结论:
- 结晶学方法可以定义对催化至关重要的功能性小蛋白质构造.
- 环素A的集体运动直接有助于其催化功率.
- 这些发现为通过蛋白质动态理解酶催化提供了一个新的框架.
更多相关视频
07:08Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues
Published on: July 14, 2015
11:27X-Ray Crystallography to Study the Oligomeric State Transition of the Thermotoga maritima M42 Aminopeptidase TmPep1050
Published on: May 13, 2020
相关概念视频
Allosteric Proteins-ATCase
Binding sites linkages can regulate a protein's function. For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...
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...
Protein Folding
Overview
Protein Organization
Proteins are polymers of amino acid residues. They are versatile and responsible for different cellular functions, including DNA replication, molecular transport, catalysis, and structural support. Proteins have a hierarchical structure comprising at least three levels of organization: primary, secondary, and tertiary structure. Some large proteins have a quaternary structure where individual protein subunits are linked together.
The primary structure of a protein is its amino acid sequence.
The primary structure of a protein is its amino acid sequence.
Protein Organization
Overview
