Wang Wei-Ning, Pan Xian-Ming, Wang Zhi-Xin
National Laboratory of Biomacromolecules, Institute of Biophysics, Academia Sinica, Beijing, PR China.
Eur J Biochem. 2004 Dec;271(23-24):4638-45. doi: 10.1111/j.1432-1033.2004.04416.x.
Limited proteolysis is a highly specific irreversible process, which can serve to initiate physiological function by converting a precursor protein into a biologically active form. When the activating enzyme and the activated enzyme coincide, the process is an autocatalytic zymogen activation (i.e. reactions in which the zymogens serves as a substrate for the corresponding active enzyme). The activity of proteases is frequently regulated by the binding of specific protease inhibitors. Thus, to understand the biological regulation of proteolysis, one must understand the role of protease inhibitors. In the present study, a detailed kinetic analysis of autocatalytic reaction modulated by a reversible inhibitor is represented. On the basis of the kinetic equation, a novel procedure is developed to evaluate the kinetic parameters of the reaction. As an example of the application of this method, effects of acetamidine, p-amidinobenzamidine and benzamidine on the autoactivation of trypsinogen by trypsin were studied.
有限蛋白水解是一个高度特异性的不可逆过程，它可以通过将前体蛋白转化为生物活性形式来启动生理功能。当激活酶和被激活的酶相同时，该过程就是自催化酶原激活（即酶原作为相应活性酶的底物的反应）。蛋白酶的活性常常受到特定蛋白酶抑制剂结合的调节。因此，要理解蛋白水解的生物学调节，就必须了解蛋白酶抑制剂的作用。在本研究中，展示了对由可逆抑制剂调节的自催化反应的详细动力学分析。基于动力学方程，开发了一种新的程序来评估该反应的动力学参数。作为该方法应用的一个例子，研究了脒基乙酰胺、对脒基苯甲脒和苯甲脒对胰蛋白酶原自激活为胰蛋白酶的影响。
