Enzyme dynamics: Looking beyond a single structure.
Enzyme dynamics: Looking beyond a single structure.
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DOI：
10.1002/cctc.202000665
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发表时间：
2020-10-06
期刊：
影响因子：
4.5
通讯作者：
Doucet N
中科院分区：
文献类型：
--
作者：
Agarwal PK;Bernard DN;Bafna K;Doucet N
对酶如何发挥作用的传统理解强烈强调结构的作用。然而，越来越多的证据清楚地表明，酶不保持固定或操作专门在或接近其天然结构。酶的不同部分（从单个残基到整个结构域）在很宽的时间尺度上进行协调运动，包括催化反应的时间尺度。迄今为止，从这些内部运动和构象波动中获得的信息已经揭示并解释了酶机制的许多方面，这些方面不能仅从单个结构来理解。尽管人们对了解酶动力学及其在催化中的作用有着广泛的兴趣，但仍然存在一些挑战。除了技术上的困难，绝大多数的研究都是在稀水溶液中进行的，其中的条件与大量酶起作用的细胞环境显著不同。在这篇评论中，我们讨论了最近的发展，一些挑战以及与此主题有关的机会。考虑动力学作为酶功能的一个组成部分的好处也可以使生物催化，工程酶的工业和医药应用的新手段。在过去的二十年里，人们对蛋白质动力学在酶催化中的作用进行了激烈的争论。从各种各样的技术和越来越多的酶复合物的证据已经收集，并出现了一个更好的图片如何内部运动和构象波动的重要贡献者的催化效率的酶。本文综述了对生物催化的基础认识以及酶工程和应用的新机遇。
Conventional understanding of how enzymes function strongly emphasizes the role of structure. However, increasing evidence clearly indicates that enzymes do not remain fixed or operate exclusively in or close to their native structure. Different parts of the enzyme (from individual residues to full domains) undergo concerted motions on a wide range of time-scales, including that of the catalyzed reaction. Information obtained on these internal motions and conformational fluctuations has so far uncovered and explained many aspects of enzyme mechanisms, which could not have been understood from a single structure alone. Although there is wide interest in understanding enzyme dynamics and its role in catalysis, several challenges remain. In addition to technical difficulties, the vast majority of investigations are performed in dilute aqueous solutions, where conditions are significantly different than the cellular milieu where a large number of enzymes operate. In this review, we discuss recent developments, several challenges as well as opportunities related to this topic. The benefits of considering dynamics as an integral part of the enzyme function can also enable new means of biocatalysis, engineering enzymes for industrial and medicinal applications. Last two decades have seen intense debate about the role of protein dynamics in enzyme catalysis. Evidence from a wide variety of techniques and for an increasing number of enzyme complexes has already been collected, and a better picture has emerged about how internal motions and conformational fluctuations are important contributors to the catalytic efficiency of enzymes. This review discusses new opportunities in fundamental understanding of biocatalysis as well as enzyme engineering and applications.
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影响因子：
64.8
作者：
Bouvignies, Guillaume;Vallurupalli, Pramodh;Hansen, D. Flemming;Correia, Bruno E.;Lange, Oliver;Bah, Alaji;Vernon, Robert M.;Dahlquist, Frederick W.;Baker, David;Kay, Lewis E.
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