Biological messiness vs. biological genius: Mechanistic aspects and roles of protein promiscuity.
Biological messiness vs. biological genius: Mechanistic aspects and roles of protein promiscuity.
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DOI：
10.1016/j.jsbmb.2014.09.010
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发表时间：
2015-07
期刊：
影响因子：
--
通讯作者：
Atkins WM
中科院分区：
文献类型：
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作者：
Atkins WM
与关注“特异性”的传统生物学范式相反，最近的研究和理论工作集中在许多生物环境中蛋白质和酶所表现出的功能性“混杂性”，包括酶解毒、类固醇生物化学、信号转导和免疫反应。此外，产生混杂的酶中间体的随机突变显然促进了不同的进化过程。反过来，中间体为进一步进化提供了机会，以优化现有蛋白质支架的新功能。在某些情况下，混杂性可能只是代表蛋白质固有的可塑性，这种可塑性源于其具有分布式构象集合的聚合性质。结合或代谢非同源底物的酶或蛋白质会在它们所参与的系统中产生“混乱”或噪音。随着我们对这些乱交行为频率的认识不断增强，了解乱交行为的分子基础并区分进化选择的乱交和进化容忍的混乱变得有趣且重要。这篇综述概述了目前对蛋白质生物化学和酶学这些方面的理解。
In contrast to the traditional biological paradigms focused on ‘specificity’, recent research and theoretical efforts have focused on functional ‘promiscuity’ exhibited by proteins and enzymes in many biological settings, including enzymatic detoxication, steroid biochemistry, signal transduction and immune responses. In addition, divergent evolutionary processes are apparently facilitated by random mutations that yield promiscuous enzyme intermediates. The intermediates, in turn, provide opportunities for further evolution to optimize new functions from existing protein scaffolds. In some cases, promiscuity may simply represent the inherent plasticity of proteins resulting from their polymeric nature with distributed conformational ensembles. Enzymes or proteins that bind or metabolize noncognate substrates create ‘messiness’ or noise in the systems they contribute to. With our increasing awareness of the frequency of these promiscuous behaviors it becomes interesting and important to understand the molecular bases for promiscuous behavior and to distinguish between evolutionarily selected promiscuity and evolutionarily tolerated messiness. This review provides an overview of current understanding of these aspects of protein biochemistry and enzymology.