Role of conformational dynamics in the evolution of novel enzyme function.
Role of conformational dynamics in the evolution of novel enzyme function.
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DOI：
10.1039/c8cc02426j
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发表时间：
2018-06-19
期刊：
影响因子：
--
通讯作者：
Osuna S
中科院分区：
文献类型：
--
作者：
Maria-Solano MA ;Serrano-Hervás E ;Romero-Rivera A ;Iglesias-Fernández J ;Osuna S
酶作为一个动态的构象集合存在，每个构象都可能在底物结合、化学转化或产物释放中发挥关键作用。我们讨论了在评价酶构象动力学及其向新功能或底物偏好进化方面的最新进展。自由能景观概念将酶描述为处于动态平衡的不同构象亚态的集合，这是评价酶活性、对映体选择性和特异性的关键。在酶序列中引入的突变可以改变原有构象状态的群体，从而强烈地改变酶适应替代底物的能力，逆转其对映体，甚至增加一些残留的混杂反应的活性。在这篇专题文章中，我们概述了目前探索酶构象自由能图景的实验和计算策略。我们提供了一系列最新的出版物，强调了构象动力学在酶向新功能和底物进化中的关键作用，并就如何在未来的计算酶设计方案中考虑构象动力学提供了一些观点。
Enzymes exist as a dynamic ensemble of conformations, each potentially playing a key role in substrate binding, the chemical transformation, or product release. We discuss recent advances in the evaluation of the enzyme conformational dynamics and its evolution towards new functions or substrate preferences. The free energy landscape concept that describes enzymes as an ensemble of differently populated conformational sub-states in dynamic equilibrium is key for evaluating enzyme activity, enantioselectivity, and specificity. Mutations introduced in the enzyme sequence can alter the populations of the pre-existing conformational states, thus strongly modifying the enzyme ability to accommodate alternative substrates, revert its enantiopreferences, and even increase the activity for some residual promiscuous reactions. In this feature article, we present an overview of the current experimental and computational strategies to explore the conformational free energy landscape of enzymes. We provide a series of recent publications that highlight the key role of conformational dynamics for the enzyme evolution towards new functions and substrates, and provide some perspectives on how conformational dynamism should be considered in future computational enzyme design protocols.
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DOI：
10.1126/science.1198542
发表时间：
2011-04-08
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bhabha G;Lee J;Ekiert DC;Gam J;Wilson IA;Dyson HJ;Benkovic SJ;Wright PE
通讯作者：
Wright PE
影响因子：
21.8
作者：
Dodani SC;Kiss G;Cahn JK;Su Y;Pande VS;Arnold FH
通讯作者：
Arnold FH
影响因子：
5.5
作者：
Contreras-Garcia, Julia;Johnson, Erin R.;Keinan, Shahar;Chaudret, Robin;Piquemal, Jean-Philip;Beratan, David N.;Yang, Weitao
通讯作者：
Yang, Weitao
影响因子：
6.8
作者：
Campbell, Eleanor C.;Correy, Galen J.;Jackson, Colin J.
通讯作者：
Jackson, Colin J.
影响因子：
8
作者：
Althoff, Eric A.;Wang, Ling;Jiang, Lin;Giger, Lars;Lassila, Jonathan K.;Wang, Zhizhi;Smith, Matthew;Hari, Sanjay;Kast, Peter;Herschlag, Daniel;Hilvert, Donald;Baker, David
通讯作者：
Baker, David