广泛的过渡状态组合作为酶催化剂的关键组成部分
Gabriel E Jara1, Francesco Pontiggia2, Renee Otten2
1Departamento de Química Inorgánica, Analítica y Química-Física (INQUIMAE-CONICET), Universidad de Buenos Aires, Buenos Aires, Argentina.
eLife
|February 18, 2025
概括
酶通过广泛的过渡状态组合 (TSE) 而不是单一结构加速反应. 这种形状的灵活性是克服酶催化过程中的性障碍的关键.
科学领域:
- 生物化学 生物化学
- 计算化学计算化学
- 结构生物学 结构生物学
背景情况:
- 过渡状态 (TS) 理论通过加速反应速度来解释酶催化.
- 蛋白质存在于形态组合中,这给独特的TS识别带来了挑战.
- 酶的转移反应,如腺酸激酶,是重要的生物过程.
研究的目的:
- 为了研究腺酸激酶中转移的酶过渡状态组合 (TSE) 的性质.
- 为了确定酶是否利用广泛的TSE来克服热瓶.
- 将计算结果与实验性酶动力学数据联系起来.
主要方法:
- 使用量子力学/分子力学 (QM/MM) 计算来建模酶反应.
- 分析反应坐标以确定过渡状态配置的范围.
- 进行了酶动力学实验,以测量激活的.
主要成果:
- 一组结构多样化和能量等价的配置定义了TSE.
- 该酶的宏观性质导致了形状外定位和不对称的TSE.
- 实验动力学证实激活的减少与广泛的TSE相一致.
结论:
- 酶使用广泛的过渡状态组合,而不是独特的结构,以实现高效的催化.
- 顺序的灵活性和移位是酶速增强的基础.
- 广泛的TSE概念统一了对蛋白质折叠,动态和功能的理解.
相关概念视频
Introduction to Mechanisms of Enzyme Catalysis
7.9K
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...
7.9K
Introduction to Enzyme Kinetics
19.6K
Enzyme kinetics studies the rates of biochemical reactions. Scientists monitor the reaction rates for a particular enzymatic reaction at various substrate concentrations. Additional trials with inhibitors or other molecules that affect the reaction rate may also be performed.
The experimenter can then plot the initial reaction rate or velocity (Vo) of a given trial against the substrate concentration ([S]) to obtain a graph of the reaction properties. For many enzymatic reactions involving a...
The experimenter can then plot the initial reaction rate or velocity (Vo) of a given trial against the substrate concentration ([S]) to obtain a graph of the reaction properties. For many enzymatic reactions involving a...
19.6K
Cooperative Allosteric Transitions
7.8K
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...
7.8K
Enzymes and Activation Energy
11.6K
The activation energy (or free energy of activation), abbreviated as Ea, is the small amount of energy input necessary for all chemical reactions to occur. During chemical reactions, certain chemical bonds break, and new ones form. For example, when a glucose molecule breaks down, bonds between the molecule's carbon atoms break. Since these are energy-storing bonds, they release energy when broken. However, the molecule must be somewhat contorted to get into a state that allows the bonds to...
11.6K
Enzyme Kinetics
95.7K
Enzymes speed up reactions by lowering the activation energy of the reactants. The speed at which the enzyme turns reactants into products is called the rate of reaction. Several factors impact the rate of reaction, including the number of available reactants. Enzyme kinetics is the study of how an enzyme changes the rate of a reaction.
Scientists typically study enzyme kinetics with a fixed amount of enzyme in the controlled environment of a test tube. When more reactant, or substrate, is...
Scientists typically study enzyme kinetics with a fixed amount of enzyme in the controlled environment of a test tube. When more reactant, or substrate, is...
95.7K
Induced-fit Model
80.1K
Most chemical reactions in cells require enzymes—biological catalysts that speed up the reaction without being consumed or permanently changed. They reduce the activation energy needed to convert the reactants into products. Enzymes are proteins, that usually work by binding to a substrate—a reactant molecule that they act upon.
Enzymes exhibit substrate specificity, meaning that they can only bind to certain substrates. This is mainly determined by the shape and chemical...
Enzymes exhibit substrate specificity, meaning that they can only bind to certain substrates. This is mainly determined by the shape and chemical...
80.1K


