Probing coupled motions in enzymatic hydrogen tunnelling reactions
Probing coupled motions in enzymatic hydrogen tunnelling reactions
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DOI：
10.1042/bst0370349
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发表时间：
2009-04-01
影响因子：
3.9
通讯作者：
Loveridge, E. Joel
中科院分区：
文献类型：
--
作者：
Allemann, Rudolf K.;Evans, Rhiannon M.;Loveridge, E. Joel
在过去的50年里，人们做了大量的工作来了解酶巨大催化能力的物理基础。然而，自然界催化剂加速化学转化的详细机制仍然难以捉摸。二氢叶酸还原酶（DHFR）是研究酶促转化的结构、功能和动力学之间关系的一个范例。一个复杂的反应级联，其中涉及重排和运动的环和域的酶，是用来定向辅因子和底物的反应性配置，从氢化物是通过量子力学隧道转移。本文综述了蛋白质动力学对TmDHFR（来自海栖热袍菌的DHFR）催化反应的化学步骤的影响的实验结果。这种酶似乎已经进化出一种最佳结构，可以在极端条件下保持催化活性构象。
Much work has gone into understanding the physical basis of the enormous catalytic power of enzymes over the last 50 years or so. Nevertheless, the detailed mechanism used by Nature's catalysts to speed chemical transformations remains elusive. DHFR (dihydrofolate reductase) has served as a paradigm to study the relationship between the structure, function and dynamics of enzymatic transformations. A complex reaction cascade, which involves rearrangements and movements of loops and domains of the enzyme, is used to orientate cofactor and substrate in a reactive configuration from which hydride is transferred by quantum mechanical tunnelling. in the present paper, we review results from experiments that probe the influence of protein dynamics on the chemical step of the reaction catalysed by TmDHFR (DHFR from Thermotoga maritima). This enzyme appears to have evolved an optimal structure that can maintain a catalytically competent conformation under extreme conditions.