PDF(Pubmed)
Abstract：
Serine proteases are members of a large family of hydrolytic enzymes in which a particular serine residue in the active site performs an essential role as a nucleophile, which is required for their proteolytic cleavage function. The array of functions performed by serine proteases is vast and includes, among others, the following: (i) the ability to fight infections; (ii) the activation of blood coagulation or blood clot lysis systems; (iii) the activation of digestive enzymes; and (iv) reproduction. Serine protease activity is highly regulated by multiple families of protease inhibitors, known collectively as the SERine Protease INhibitor (SERPIN). The serpins use a conformational change mechanism to inhibit proteases in an irreversible way. The unusual conformational change required for serpin function provides an elegant opportunity for allosteric regulation by the binding of cofactors, of which the most well-studied is heparin. The goal of this review is to discuss some of the clinically relevant serine protease-serpin interactions that may be enhanced by heparin or other negatively charged polysaccharides. The paired serine protease-serpin in the framework of heparin that we review includes the following: thrombin-antithrombin III, plasmin-anti-plasmin, C1 esterase/kallikrein-C1 esterase inhibitor, and furin/TMPRSS2 (serine protease Transmembrane Protease 2)-alpha-1-antitrypsin, with the latter in the context of COVID-19 and prostate cancer.
摘要：
丝氨酸蛋白酶是水解酶大家族的成员，其中活性位点中的特定丝氨酸残基作为亲核试剂发挥重要作用。这是它们的蛋白水解切割功能所必需的。由丝氨酸蛋白酶执行的一系列功能是广泛的，包括，其中,以下:(i)抵抗感染的能力;(ii)凝血或血凝块溶解系统的活化;(iii)消化酶的活化;和(iv)繁殖。丝氨酸蛋白酶活性受多个家族的蛋白酶抑制剂高度调节，统称为丝氨酸蛋白酶抑制剂（SERPIN）。serpin使用构象变化机制以不可逆的方式抑制蛋白酶。serpin功能所需的异常构象变化为通过辅因子的结合进行变构调节提供了一个优雅的机会，其中研究最充分的是肝素。这篇综述的目的是讨论一些临床相关的丝氨酸蛋白酶-丝氨酸蛋白酶相互作用，这些相互作用可能被肝素或其他带负电荷的多糖增强。我们审查的肝素框架中的成对丝氨酸蛋白酶-丝氨酸蛋白酶包括以下内容：凝血酶-抗凝血酶III，纤溶酶-抗纤溶酶,C1酯酶/激肽释放酶-C1酯酶抑制剂，和弗林蛋白酶/TMPRSS2（丝氨酸蛋白酶跨膜蛋白酶2）-α-1-抗胰蛋白酶，与后者在COVID-19和前列腺癌的背景下。
