Hydrogen tunneling links protein dynamics to enzyme catalysis.
Hydrogen tunneling links protein dynamics to enzyme catalysis.
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DOI：
10.1146/annurev-biochem-051710-133623
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发表时间：
2013
影响因子：
16.6
通讯作者：
Kohen A
中科院分区：
文献类型：
--
作者：
Klinman JP;Kohen A
蛋白质动力学和功能之间的关系是当代相当感兴趣的主题。虽然在配体结合和释放步骤中经常观察到蛋白质运动，但蛋白质运动对键形成/断裂过程的催化作用的贡献更难以探测和验证。在这里，我们展示了与酶促C-H键裂解相关的量子力学氢隧穿如何为实现最佳催化的蛋白质动力学的必要性提供了一个独特的窗口。实验结果支持一个层次的控制H-供体和受体的距离和活性位点的静电，创造一个适合H-隧穿的构象合奏的mandically平衡的运动。这一观点的一个可能的扩展甲基转移和其他催化反应也提出。了解这些动态的概念框架上的酶活性，抑制剂/药物设计，仿生催化剂设计的影响可能是巨大的。
The relationship between protein dynamics and function is a subject of considerable contemporary interest. Although protein motions are frequently observed during ligand binding and release steps, the contribution of protein motions to the catalysis of bond making/breaking processes is more difficult to probe and verify. Here, we show how the quantum mechanical hydrogen tunneling associated with enzymatic C–H bond cleavage provides a unique window into the necessity of protein dynamics for achieving optimal catalysis. Experimental findings support a hierarchy of thermodynamically equilibrated motions that control the H-donor and -acceptor distance and active-site electrostatics, creating an ensemble of conformations suitable for H-tunneling. A possible extension of this view to methyl transfer and other catalyzed reactions is also presented. The impact of understanding these dynamics on the conceptual framework for enzyme activity, inhibitor/drug design, and biomimetic catalyst design is likely to be substantial.
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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：
15
作者：
Bandaria JN;Cheatum CM;Kohen A
通讯作者：
Kohen A
影响因子：
3.3
作者：
Antoniou, Dimitri;Schwartz, Steven D.
通讯作者：
Schwartz, Steven D.
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：
18.3
作者：
CLELAND, WW
通讯作者：
CLELAND, WW