Catalytic efficiency of enzymes: a theoretical analysis.
Catalytic efficiency of enzymes: a theoretical analysis.
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DOI：
10.1021/bi301515j
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发表时间：
2013-03-26
期刊：
影响因子：
2.9
通讯作者：
Hammes-Schiffer S
中科院分区：
文献类型：
--
作者：
Hammes-Schiffer S
这篇简短的综述分析了酶催化的基本物理原理，重点强调了酶的平衡运动和构象采样的作用。这些概念是在三个具有代表性的体系的背景下展开的，即二氢叶酸还原酶、酮类固醇异构酶和大豆脂氧合酶。所有这些反应都涉及氢转移，但所讨论的许多概念具有更普遍的适用性。本综述分析的因素包括氢隧穿、质子供体 - 受体运动、氢键、pKa偏移、静电作用、预组织、重组织和构象运动。化学步骤的速率常数主要由自由能垒决定，而自由能垒与有利于化学反应的构象采样概率相关。根据这一观点，随机热运动导致酶和配体发生平衡构象变化，从而产生有利于化学键断裂和形成的构象。对于质子、氢负离子以及质子耦合电子转移反应，通常供体和受体之间的距离会拉近以促进转移。突变对催化速率常数的影响可以用上述列举的因素来解释。特别是远端突变可以改变酶的构象运动，从而改变有利于化学反应的构象采样概率。诸如振动斯塔克光谱等方法，通过在酶中特异性地引入对环境敏感的探针，并结合实验和理论计算，为酶催化的这些方面提供了更深入的见解。
This brief review analyzes the underlying physical principles of enzyme catalysis, with an emphasis on the role of equilibrium enzyme motions and conformational sampling. The concepts are developed in the context of three representative systems, namely dihydrofolate reductase, ketosteroid isomerase, and soybean lipoxygenase. All of these reactions involve hydrogen transfer, but many of the concepts discussed are more generally applicable. The factors that are analyzed in this review include hydrogen tunneling, proton donor-acceptor motion, hydrogen bonding, pKa shifting, electrostatics, preorganization, reorganization, and conformational motions. The rate constant for the chemical step is determined primarily by the free energy barrier, which is related to the probability of sampling configurations conducive to the chemical reaction. According to this perspective, stochastic thermal motions lead to equilibrium conformational changes in the enzyme and ligands that result in configurations favorable to the breaking and forming of chemical bonds. For proton, hydride, and proton-coupled electron transfer reactions, typically the donor and acceptor become closer to facilitate the transfer. The impact of mutations on the catalytic rate constants can be explained in terms of the factors enumerated above. In particular, distal mutations can alter the conformational motions of the enzyme and therefore the probability of sampling configurations conducive to the chemical reaction. Methods such as vibrational Stark spectroscopy, in which environmentally sensitive probes are introduced site-specifically in the enzyme, provide further insight into these aspects of enzyme catalysis through a combination of experiments and theoretical calculations.
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影响因子：
56.9
作者：
Boehr, David D.;McElheny, Dan;Wright, Peter E.
通讯作者：
Wright, Peter E.
影响因子：
15
作者：
Hatcher, E;Soudackov, AV;Hammes-Schiffer, S
通讯作者：
Hammes-Schiffer, S
影响因子：
4.4
作者：
Billeter, SR;Webb, SP;Hammes-Schiffer, S
通讯作者：
Hammes-Schiffer, S
影响因子：
2.9
作者：
Chakravorty, Dhruva K.;Soudackov, Alexander V.;Hammes-Schiffer, Sharon
通讯作者：
Hammes-Schiffer, Sharon
DOI：
10.1073/pnas.0914163107
发表时间：
2010-01-26
影响因子：
11.1
作者：
Boehr, David D.;McElheny, Dan;Wright, Peter E.
通讯作者：
Wright, Peter E.