Allemann Rudolf K, Evans Rhiannon M, Loveridge E Joel
School of Chemistry, Cardiff University, Cardiff, UK.
Biochem Soc Trans. 2009 Apr;37(Pt 2):349-53. doi: 10.1042/BST0370349.
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.
在过去约50年里，人们为理解酶的巨大催化能力的物理基础付出了诸多努力。然而，大自然的催化剂加速化学转化所采用的详细机制仍然难以捉摸。二氢叶酸还原酶（DHFR）一直作为研究酶促转化的结构、功能和动力学之间关系的范例。一个复杂的反应级联，涉及酶的环和结构域的重排与移动，用于将辅因子和底物定向成反应性构型，在此构型下氢化物通过量子力学隧穿进行转移。在本文中，我们综述了一些实验结果，这些实验探究了蛋白质动力学对嗜热栖热菌二氢叶酸还原酶（TmDHFR）催化反应的化学步骤的影响。这种酶似乎进化出了一种最佳结构，能够在极端条件下维持催化活性构象。
