The transition of prothrombin to thrombin.
The transition of prothrombin to thrombin.
复制标题
凝血酶原向凝血酶的过渡。
DOI：
10.1111/jth.12217
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发表时间：
2013-06
期刊：
影响因子：
--
通讯作者：
Krishnaswamy S
中科院分区：
文献类型：
--
作者：
Krishnaswamy S
凝血酶原酶催化的凝血酶原蛋白水解转化为凝血酶是血液凝固中研究最广泛的反应之一。在该领域的早期，人们对这种反应的参与者进行了复杂的生物物理和生物化学见解。然而，许多基本的酶学问题仍然没有答案。我总结了新的发展，揭示了高底物特异性实现的机制，以及这些策略对酶功能的影响。出现了两个原则，它们偏离了在该领域占主导地位的传统智慧。1)酶的特异性主要是由底物和酶之间的外位点结合相互作用的贡献，而不是由特异性识别侧翼序列的易裂键。再加上作为酶原到蛋白酶转变的结果的底物构象的调节，对酶功能的许多方面产生了新的机理见解。2)酶原蛋白酶裂解后的过渡不是绝对的，相反，凝血酶可以可逆地相互转化的酶原样和蛋白酶样的形式取决于它结合的配体的互补性。这建立了新的范例，考虑蛋白酶变构和酶的功能如何可能被调制的配体结合。凝血酶原酶对凝血酶原的作用的这些见解对于理解血液凝固的功能具有广泛的意义。
The proteolytic conversion of prothrombin to thrombin catalysed by prothrombinase is one of the more extensively studied reactions of blood coagulation. Sophisticated biophysical and biochemical insights into the players of this reaction were developed in the early days of the field. Yet, many basic enzymological questions remained unanswered. I summarise new developments that uncover mechanisms by which high substrate specificity is achieved, and the impact of these strategies on enzymic function. Two principles emerge that deviate from conventional wisdom that has otherwise dominated thinking in the field. 1) Enzymic specificity is dominated by the contribution of exosite binding interactions between substrate and enzyme rather than by specific recognition of sequences flanking the scissile bond. Coupled with the regulation of substrate conformation as a result of the zymogen to proteinase transition, novel mechanistic insights result for numerous aspects of enzyme function. 2) The transition of zymogen to proteinase following cleavage is not absolute and instead, thrombin can reversibly interconvert between zymogen-like and proteinase-like forms depending on the complement of ligands bound to it. This establishes new paradigms for considering proteinase allostery and how enzyme function may be modulated by ligand binding. These insights into the action of prothrombinase on prothrombin have wide-ranging implications for the understanding of function in blood coagulation.
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影响因子：
4.8
作者：
Baugh, RJ;Dickinson, CD;Krishnaswamy, S
通讯作者：
Krishnaswamy, S
影响因子：
4.8
作者：
Brufatto, N;Nesheim, ME
通讯作者：
Nesheim, ME
影响因子：
4.8
作者：
Anderson, PJ;Nesset, A;Bock, PE
通讯作者：
Bock, PE
影响因子：
4.8
作者：
Anderson, PJ;Bock, PE
通讯作者：
Bock, PE
影响因子：
4.8
作者：
Bah, Alaji;Carrell, Christopher J.;Di Cera, Enrico
通讯作者：
Di Cera, Enrico