过渡状态稳定作为抗体催化效率的衡量标准
1Department of Chemistry, University of Florida, Gainesville 32611, USA.
Nature
|June 1, 1995
概括
催化抗体加速化学反应,即使是动力学上不利的化学反应. 它们的速度加速是可以使用过渡状态理论和结合常数来预测的,为抗体和酶催化提供了洞察力.
科学领域:
- 生物化学 生物化学
- 化学催化剂的化学催化剂
- 免疫学 免疫学 免疫学
背景情况:
- 单克隆抗体在约60个反应中表现出催化活性.
- 早期的例子集中在动力学上有利的反应,如水解.
- 最近的发现表明,抗体可以加速动力学上不利的路径.
研究的目的:
- 用过渡状态理论量化分析抗体催化剂的范围和局限性.
- 开发一种用于抗体催化反应中的速率加速的预测模型.
- 将抗体催化机制与酶的催化机制进行比较.
主要方法:
- 过渡状态理论用于定量分析的应用.
- 根据约束常数计算速度加速的计算.
- 基质和过渡状态模拟结合亲和力的比较.
主要成果:
- 观察到的速度加速可以准确地预测.
- 平衡结合常数的比率是预测的关键.
- 该模型合理化了不利反应中的产品选择性.
结论:
- 过渡状态理论为理解抗体催化提供了一个框架.
- 预测模型可以估计催化抗体的潜在速度加速.
- 抗体和酶催化机制之间存在关键差异.
更多相关视频
15:27Determination of High-affinity Antibody-antigen Binding Kinetics Using Four Biosensor Platforms
Published on: April 17, 2017
10:17Creating Highly Specific Chemically Induced Protein Dimerization Systems by Stepwise Phage Selection of a Combinatorial Single-Domain Antibody Library
Published on: January 14, 2020
相关概念视频
Catalysis
The presence of a catalyst affects the rate of a chemical reaction. A catalyst is a substance that can increase the reaction rate without being consumed during the process. A basic comprehension of a catalysts’ role during chemical reactions can be understood from the concept of reaction mechanisms and energy diagrams.
The Equilibrium Binding Constant and Binding Strength
The equilibrium binding constant (Kb) quantifies the strength of a protein-ligand interaction. Kb can be calculated as follows when the reaction is at equilibrium:
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...
Catalytically Perfect Enzymes
The theory of catalytically perfect enzymes was first proposed by W.J. Albery and J. R. Knowles in 1976. These enzymes catalyze biochemical reactions at high-speed. Their catalytic efficiency values range from 108-109 M-1s-1. These enzymes are also called 'diffusion-controlled' as the only rate-limiting step in the catalysis is that of the substrate diffusion into the active site. Examples include triose phosphate isomerase, fumarase, and superoxide dismutase.
Introduction to Mechanisms of Enzyme Catalysis
For many years, scientists thought that enzyme-substrate binding took place in a simple "lock-and-key" fashion. This model stated that the enzyme and substrate fit together perfectly in one instantaneous step. However, current research supports a more refined view scientists call induced fit. The induced-fit model expands upon the lock-and-key model by describing a more dynamic interaction between enzyme and substrate. As the enzyme and substrate come together, their interaction causes a mild...
Transition State Theory
Transition-state theory, also known as activated-complex theory, provides a molecular-level explanation of reaction rates in both gas-phase and solution-phase reactions. It extends earlier kinetic models by considering the formation of a short-lived, high-energy configuration during a reaction.The progress of a chemical reaction can be represented using a reaction profile, which plots potential energy against the reaction coordinate. As two reactant molecules approach one another, their...
