At the dawn of the 21st century: Is dynamics the missing link for understanding enzyme catalysis?
At the dawn of the 21st century: Is dynamics the missing link for understanding enzyme catalysis?
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DOI：
10.1002/prot.22654
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发表时间：
2010-05-01
影响因子：
2.9
通讯作者：
Warshel, Arieh
中科院分区：
文献类型：
--
作者：
Kamerlin, Shina C. L.;Warshel, Arieh
关键词：
酶在几乎所有的生物过程中都起着关键作用，加速各种代谢反应，控制能量转导，遗传信息的转录和翻译，以及信号传导。与未催化的反应相比，它们具有显著的加速反应的能力，使原本在生物相关时间尺度上不会发生的关键过程成为可能。因此，在分子水平上理解酶的催化能力具有广泛的兴趣。为了解释这一现象，人们提出了几个建议，其中一个在近年来得到迅速发展的观点是，酶动力学在某种程度上有助于催化。这篇综述以一种批判性的方式考察了动力学的提议，基本上考虑了所有合理的定义，包括（但不限于）诸如“构象和化学运动之间的耦合”、“景观搜索”和“熵通道”等提议的效应。结果表明，这些提出的效应都没有被实验证明有助于催化，也没有得到一致的理论研究的支持。另一方面，需要澄清的是，仔细的模拟研究已经排除了大多数（如果不是全部的话）动力学建议。这篇综述的重点是澄清不同催化建议的逻辑定义的作用，以及根据假设的潜在表面和反应坐标进行明确表述的必要性。最后指出，通过激活自由能的相应变化，静电预组织实际上解释了酶所观察到的催化作用。
Enzymes play a key role in almost all biological processes, accelerating a variety of metabolic reactions as well as controlling energy transduction, transcription and translation of genetic information, and signaling. They possess the remarkable capacity to accelerate reactions by many orders of magnitude compared to their uncatalyzed counterparts, making feasible crucial processes that would otherwise not occur on biologically relevant timescales. Thus, there is broad interest in understanding the catalytic power of enzymes on a molecular level. Several proposals have been put forward to try to explain this phenomenon, and one that has rapidly gained momentum in recent years is the idea that enzyme dynamics somehow contributes to catalysis. This review examines the dynamical proposal in a critical way considering basically all reasonable definitions, including (but not limited to) such proposed effects as “coupling between conformational and chemical motions”, “landscape searches” and “entropy funnels”. It is shown that none of these proposed effects have been experimentally demonstrated to contribute to catalysis, nor are they supported by consistent theoretical studies. On the other hand, it is clarified that careful simulation studies have excluded most (if not all) dynamical proposals. This review places significant emphasis on clarifying the role of logical definitions of different catalytic proposals, and on the need for a clear formulation in terms of the assumed potential surface and reaction coordinate. Finally, it is pointed out that electrostatic preorganization actually accounts for the observed catalytic effects of enzymes, through the corresponding changes in the activation free energies.
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DOI：
10.1073/pnas.94.24.12797
发表时间：
1997-11-25
影响因子：
11.1
作者：
Bahnson, BJ;Colby, TD;Klinman, JP
通讯作者：
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影响因子：
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影响因子：
15
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影响因子：
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作者：
Antoniou, D;Schwartz, SD
通讯作者：
Schwartz, SD
影响因子：
3.3
作者：
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通讯作者：
Go, N