Pike Robert N, Buckle Ashley M, le Bonniec Bernard F, Church Frank C
Department of Biochemistry & Molecular Biology, Monash University, Clayton, Victoria, Australia.
FEBS J. 2005 Oct;272(19):4842-51. doi: 10.1111/j.1742-4658.2005.04880.x.
Members of the serine protease inhibitor (serpin) superfamily play important roles in the inhibition of serine proteases involved in complex systems. This is evident in the regulation of coagulation serine proteases, especially the central enzyme in this system, thrombin. This review focuses on three serpins which are known to be key players in the regulation of thrombin: antithrombin and heparin cofactor II, which inhibit thrombin in its procoagulant role, and protein C inhibitor, which primarily inhibits the thrombin/thrombomodulin complex, where thrombin plays an anticoagulant role. Several structures have been published in the past few years which have given great insight into the mechanism of action of these serpins and have significantly added to a wealth of biochemical and biophysical studies carried out previously. A major feature of these serpins is that they are under the control of glycosaminoglycans, which play a key role in accelerating and localizing their action. While further work is clearly required to understand the mechanism of action of the glycosaminoglycans, the biological mechanisms whereby cognate glycosaminoglycans for each serpin come into contact with the inhibitors also requires much further work in this important field.
丝氨酸蛋白酶抑制剂（serpin）超家族成员在抑制参与复杂系统的丝氨酸蛋白酶方面发挥着重要作用。这在凝血丝氨酸蛋白酶的调节中很明显，尤其是该系统的核心酶——凝血酶。本综述聚焦于三种已知在凝血酶调节中起关键作用的丝氨酸蛋白酶抑制剂：抗凝血酶和肝素辅因子II，它们抑制发挥促凝作用的凝血酶；以及蛋白C抑制剂，它主要抑制凝血酶/血栓调节蛋白复合物，在该复合物中凝血酶发挥抗凝作用。在过去几年中已经发表了几种结构，这些结构极大地深入揭示了这些丝氨酸蛋白酶抑制剂的作用机制，并显著补充了先前进行的大量生物化学和生物物理学研究。这些丝氨酸蛋白酶抑制剂的一个主要特征是它们受糖胺聚糖的控制，糖胺聚糖在加速和定位其作用方面起关键作用。虽然显然需要进一步开展工作来了解糖胺聚糖的作用机制，但在这个重要领域，每种丝氨酸蛋白酶抑制剂的同源糖胺聚糖与抑制剂接触的生物学机制也需要开展更多工作。
