Kinetic isotope effects in the characterization of catalysis by protein tyrosine phosphatases.
Kinetic isotope effects in the characterization of catalysis by protein tyrosine phosphatases.
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DOI：
10.1016/j.bbapap.2015.03.010
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发表时间：
2015-11
期刊：
影响因子：
--
通讯作者：
Hengge AC
中科院分区：
文献类型：
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作者：
Hengge AC
虽然在生物学上是有利的，但磷酸单酯的非催化水解是非常缓慢的，使得磷酸酶成为已知的催化效率最高的酶之一。蛋白质酪氨酸磷酸酶（Protein-tyrosine phosphatases，PTPs）广泛存在于生物学中，动力学同位素效应是研究PTPs催化机制和磷酰基转移过渡态的重要工具。后来，KIE提供的独特细节水平导致了关于蛋白质运动在PTP催化中的潜在作用的更深层次的问题。最近的发现，这种运动是负责不同的催化速率之间的PTP产生的问题，从KIE数据表明，过渡态和化学机制是相同的，结合结构数据证明重叠的活性位点。KIE还揭示了过渡态的扰动，因为突变直接涉及化学的残基，以及影响催化所必需的蛋白质运动的残基。
Although thermodynamically favorable, the uncatalyzed hydrolysis of phosphate monoesters is extraordinarily slow, making phosphatases among the most catalytically efficient enzymes known. Protein-tyrosine phosphatases (PTPs) are ubiquitous in biology, and kinetic isotope effects were one of the key mechanistic tools used to discern molecular details of their catalytic mechanism and the transition state for phosphoryl transfer. Later, the unique level of detail KIEs provided led to deeper questions about the potential role of protein motions in PTP catalysis. The recent discovery that such motions are responsible for different catalytic rates between PTPs arose from questions originating from KIE data showing that the transition states and chemical mechanisms are identical, combined with structural data demonstrating superimposable active sites. KIEs also reveal perturbations to the transition state as mutations are made to residues directly involved in chemistry, and to residues that affect protein motions essential for catalysis.