Chemistry and mechanism of phosphatases, diesterases and triesterases.
Chemistry and mechanism of phosphatases, diesterases and triesterases.
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磷酸酶、二酯酶和三酯酶的化学和机制。
DOI：
10.1016/j.bbapap.2012.09.013
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Hengge,AlvanC
中科院分区：
文献类型：
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作者：
Hengge,AlvanC
1987年，已故的Frank Westheimer为《科学》杂志写了一篇题为《为什么大自然选择磷酸盐》的文章。Westheimer总结了磷酸酯和酸酐的独特化学性质，使其在生物学的许多方面发挥独特的作用，从高度稳定的核酸到富含能量的分子，如ATP，以及许多磷酸化的中间代谢物和小分子。当时，普遍存在的作用，磷酸化的调节，介导的协同活动的激酶和磷酸酶，尚未得到重视。磷酸酯的稳定性使其非常适合在生物学中发挥作用。物理有机化学家已经表明，磷酸单酯的水解，特别是大多数磷酸酶的底物二价阴离子的水解，是生物相关的最慢的非催化反应之一，尽管在生物学上是有利的[2]。因此，就相对于相应的非催化反应的酶促速率而言，磷酸酶是已知的最具催化活性的酶中的一些。已经有相当多的研究致力于辨别磷酸酯在溶液中和通过酶反应的机理。随着近几十年来知识的进步，这些结果定期总结在综述中[3-9]。最近的综述全面总结了我们目前对磷酰基转移机制的理解，酶如何催化这些反应，以及用于回答这些问题的机械工具。Lassila等人在2011年的综述中以非专业人士可以理解的方式解释了该领域的核心问题和机械分析中使用的方法，同时还详尽地回顾和讨论了大量的实验数据[9]。这一特殊部分的文章描述和分析了非催化反应以及磷酸酶、磷酸二酯酶和磷酸三酯酶的酶促反应的最新进展。
In 1987 the late Frank Westheimer wrote an article for Science magazine entitled,“Why Nature Chose Phosphates”[1]. Westheimer summarized the unique chemistry of phosphate esters and anhydrides that uniquely suited them for roles in many aspects of biology, from highly stable nucleic acids, to energy rich molecules like ATP, and a host of phosphorylated intermediate metabolites and small molecules. At that time the ubiquitous role of phosphorylation in regulation, mediated by the synergistic activities of kinases and phosphatases, was not yet appreciated. The remarkable stability of phosphate esters makes them well suited for their roles in biology.Physical organic chemists have shown that the hydrolysis of phosphate monoesters, particularly the dianions that are the substrates of most phosphatases, is one of the slowest uncatalyzed reactions of biological relevance, despite being thermodynamically favorable [2]. As a result, phosphatases are some of the most catalytically proficient enzymes known, in terms of enzymatic rates relative to the corresponding uncatalyzed reaction. Considerable study has been devoted to discerning the mechanisms by which phosphate esters react both in solution, and by enzymes. The results have been periodically summarized in reviews as knowledge has advanced in recent decades [3–9]. The more recent reviews give comprehensive summaries of our current understanding of the mechanisms of phosphoryl transfer, how enzymes catalyze these reactions, and of the mechanistic tools used to answer these questions. The 2011 review by Lassila et al. does a particularly good job of explaining the central questions in the field and the methodologies used in mechanistic analysis, in a way that is accessible to non-specialists, while also exhaustively reviewing and discussing a very large body of experimental data [9]. The articles in this special section describe and analyze recent developments in uncatalyzed reactions, as well as enzymatic reactions of phosphatases, phosphodiesterases, and phosphotriesterases.