Biological phosphoryl-transfer reactions: understanding mechanism and catalysis.

Biological phosphoryl-transfer reactions: understanding mechanism and catalysis.
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DOI:
10.1146/annurev-biochem-060409-092741
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发表时间:
2011
影响因子:
16.6
通讯作者:
Herschlag D
Herschlag D
中科院分区:
生物学1区
文献类型:
--
作者:
Lassila JK;Zalatan JG;Herschlag D

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磷酰基转移反应是生物学的核心。这些反应还具有一些最慢的非酶速率,因此需要生物催化剂的巨大速率加速。尽管磷酰基转移具有核心重要性,并且它带来了令人着迷的催化挑战,但人们对这些反应的性质仍然存在很大的困惑。尽管对这些反应背后的化学机制进行了数十年的研究,但这种混乱仍然存在。在这里,我们回顾磷酰基转移反应,目的是为读者提供概念和实验背景,以理解这项工作,评估新的结果和建议,并将这种理解应用于酶。我们描述了一些争议的可能解决方案,同时强调了我们当前方法和理解的局限性。我们将这种理解应用于酶催化的磷酰基转移,并提供说明性示例来说明这种机械背景如何指导和加深我们对酶及其作用机制的理解。最后,我们提出了该领域未来的重要挑战。
Phosphoryl-transfer reactions are central to biology. These reactions also have some of the slowest nonenzymatic rates and thus require enormous rate accelerations from biological catalysts. Despite the central importance of phosphoryl transfer and the fascinating catalytic challenges it presents, substantial confusion persists about the properties of these reactions. This confusion exists despite decades of research on the chemical mechanisms underlying these reactions. Here we review phosphoryl-transfer reactions with the goal of providing the reader with the conceptual and experimental background to understand this body of work, to evaluate new results and proposals, and to apply this understanding to enzymes. We describe likely resolutions to some controversies, while emphasizing the limits of our current approaches and understanding. We apply this understanding to enzyme-catalyzed phosphoryl transfer and provide illustrative examples of how this mechanistic background can guide and deepen our understanding of enzymes and their mechanisms of action. Finally, we present important future challenges for this field.
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