Directed Evolution's Influence on Rapid Density Fluctuations Illustrates How Protein Dynamics Can Become Coupled to Chemistry.
Directed Evolution's Influence on Rapid Density Fluctuations Illustrates How Protein Dynamics Can Become Coupled to Chemistry.
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DOI：
10.1021/acscatal.0c01618
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发表时间：
2020-08-07
期刊：
影响因子：
12.9
通讯作者：
Schwartz SD
中科院分区：
文献类型：
--
作者：
Schafer JW;Schwartz SD
蛋白质工程是一个不断发展的领域，有多种实验技术可用于改变蛋白质功能。然而，从头创造酶仍处于起步阶段，到目前为止产生的酶催化效率适中。在这项研究中，检查了一种人工逆醛缩酶系统，该系统具有与蛋白质动力学耦合的化学作用。最初的设计是通过计算创建的，然后对该蛋白质进行定向进化以改善最初的低催化效率。我们发现，这种酶的重新设计导致整个酶通过氢键网络的改变而被重塑，导致密度快速波动。这项工作还导致了第二个重要动议的发现，该动议有助于中间产品的发布。这些结果提供了令人信服的证据，表明为了设计高效的蛋白质催化剂，需要在设计中考虑快速蛋白质动力学。
Protein engineering is a growing field with a variety of experimental techniques available for altering protein function. However, creating an enzyme de novo is still in its infancy, so far yielding enzymes of modest catalytic efficiency. In this study, a system of artificial retro-aldolase enzymes found to have chemistry coupled to protein dynamics was examined. The original design was created computationally, and this protein was then subjected to directed evolution to improve the initial low catalytic efficiency. We found that this re-engineering of the enzyme resulted in rapid density fluctuations throughout the enzyme being reshaped via alterations in the hydrogen bonding network. This work also led to the discovery of a second important motion which aids in the release of an intermediate product. These results provide compelling evidence that to engineer efficient protein catalysts, fast protein dynamics need to be considered in the design.
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DOI：
10.1073/pnas.1706849114
发表时间：
2017-11-07
影响因子：
11.1
作者：
Akiva E;Copp JN;Tokuriki N;Babbitt PC
通讯作者：
Babbitt PC
影响因子：
3
作者：
BROOKS, BR;BRUCCOLERI, RE;KARPLUS, M
通讯作者：
KARPLUS, M
影响因子：
14.8
作者：
Giger L;Caner S;Obexer R;Kast P;Baker D;Ban N;Hilvert D
通讯作者：
Hilvert D
影响因子：
64.8
作者：
Esvelt, Kevin M.;Carlson, Jacob C.;Liu, David R.
通讯作者：
Liu, David R.
影响因子：
7.7
作者：
Dougherty, Michael J.;Arnold, Frances H.
通讯作者：
Arnold, Frances H.