The Moderately Efficient Enzyme: Evolutionary and Physicochemical Trends Shaping Enzyme Parameters
The Moderately Efficient Enzyme: Evolutionary and Physicochemical Trends Shaping Enzyme Parameters
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DOI：
10.1021/bi2002289
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发表时间：
2011-05-31
期刊：
影响因子：
2.9
通讯作者：
Milo, Ron
中科院分区：
文献类型：
--
作者：
Bar-Even, Arren;Noor, Elad;Milo, Ron
酶的动力学参数是了解大多数生物过程的速率和特异性的关键。尽管经常研究单个酶的特定趋势，但很少关注全局趋势。我们对从文献中收集的数千种酶的 k(cat) 和 K-M 值进行了分析。我们发现“平均酶”表现出类似于 10 s(-1) 的 k(cat) 和类似于 10(5) s(-1) M-1 的 k(cat)/K-M，远低于扩散极限和动力学优越酶的特征教科书描述。为什么大多数酶表现出中等催化效率？在预期选择压力较弱的情况下，最高比率可能不会变化。例如，我们发现，次级代谢中的酶平均比中枢代谢中的酶慢 30 倍。我们还发现有迹象表明底物的物理化学性质会影响动力学参数。具体来说，低分子量和疏水性似乎限制了 K-M 优化。因此，用磷酸盐、Colt 或其他大修饰剂进行取代会显着降低利用取代底物的酶的 K-M 值。因此，进化选择压力和物理化学约束似乎共同塑造了酶的动力学参数。在许多情况下，一些酶对其天然底物的催化效率似乎也可能通过自然或实验室进化而提高。
The kinetic parameters of enzymes are key to understanding the rate and specificity of most biological processes. Although specific trends are frequently studied for individual enzymes, global trends are rarely addressed. We performed an analysis of k(cat) and K-M values of several thousand enzymes collected from the literature. We found that the "average enzyme" exhibits a k(cat) of similar to 10 s(-1) and a k(cat)/K-M of similar to 10(5) s(-1) M-1, much below the diffusion limit and the characteristic textbook portrayal of kinetically superior enzymes. Why do most enzymes exhibit moderate catalytic efficiencies? Maximal rates may not evolve in cases where weaker selection pressures are expected. We find, for example, that enzymes operating in secondary metabolism are, on average, similar to 30-fold slower than those of central metabolism. We also find indications that the physicochemical properties of substrates affect the kinetic parameters. Specifically, low molecular mass and hydrophobicity appear to limit K-M optimization. In accordance, substitution with phosphate, Colt, or other large modifiers considerably lowers the K-M values of enzymes utilizing the substituted substrates. It therefore appears that both evolutionary selection pressures and physicochemical constraints shape the kinetic parameters of enzymes. It also seems likely that the catalytic efficiency of some enzymes toward their natural substrates could be increased in many cases by natural or laboratory evolution.