Huntington James A
Department of Haematology, University of Cambridge, Cambridge Institute for Medical Research, Wellcome Trust/MRC Building, Cambridge, UK.
Biochim Biophys Acta. 2012 Jan;1824(1):246-52. doi: 10.1016/j.bbapap.2011.07.005. Epub 2011 Jul 18.
Thrombin is the final protease generated in the blood coagulation cascade. It has multiple substrates and cofactors, and serves both pro- and anti-coagulant functions. How thrombin activity is directed throughout the evolution of a clot and the role of conformational change in determining thrombin specificity are issues that lie at the heart of the haemostatic balance. Over the last 20 years there have been a great number of studies supporting the idea that thrombin is an allosteric enzyme that can exist in two conformations differing in activity and specificity. However, recent work has shown that thrombin in its unliganded state is inherently flexible in regions that are important for activity. The effect of flexibility on activity is discussed in this review in context of the zymogen-to-protease conformational transition. Understanding thrombin function in terms of 'plasticity' provides a new conceptual framework for understanding regulation of enzyme activity in general. This article is part of a Special Issue entitled: Proteolysis 50 years after the discovery of lysosome.
凝血酶是血液凝固级联反应中产生的最终蛋白酶。它有多种底物和辅因子，并具有促凝血和抗凝血功能。在血凝块形成的整个过程中，凝血酶活性是如何被引导的，以及构象变化在决定凝血酶特异性方面所起的作用，是止血平衡的核心问题。在过去20年里，有大量研究支持凝血酶是一种别构酶的观点，它可以以两种活性和特异性不同的构象存在。然而，最近的研究表明，未结合配体状态的凝血酶在对活性至关重要的区域本质上是灵活的。在本综述中，将在酶原到蛋白酶的构象转变背景下讨论灵活性对活性的影响。从“可塑性”角度理解凝血酶功能，为总体理解酶活性调节提供了一个新的概念框架。本文是名为：溶酶体发现50年后的蛋白水解的特刊的一部分。
