Chandrasekharan U M, Sanker S, Glynias M J, Karnik S S, Husain A
Department of Molecular Cardiology, Cleveland Clinic Foundation, OH 44195, USA.
Science. 1996 Jan 26;271(5248):502-5. doi: 10.1126/science.271.5248.502.
The current model of serine protease diversity theorizes that the earliest protease molecules were simple digestive enzymes that gained complex regulatory functions and restricted substrate specificities through evolution. Among the chymase group of serine proteases are enzymes that convert angiotensin I to angiotensin II, as well as others that simply degrade angiotensins. An ancestral chymase reconstructed with the use of phylogenetic inference, total gene synthesis, and protein expression had efficient and specific angiotensin II-forming activity (turnover number, about 700 per second). Thus, angiotensin II-forming activity is the more primitive state for chymases, and the loss of such activity occurred later in the evolution of some of these serine proteases.
目前丝氨酸蛋白酶多样性的模型推测，最早的蛋白酶分子是简单的消化酶，它们在进化过程中获得了复杂的调节功能并限制了底物特异性。在丝氨酸蛋白酶的糜酶组中，有些酶可将血管紧张素I转化为血管紧张素II，还有一些则只是降解血管紧张素。通过系统发育推断、全基因合成和蛋白质表达重建的一种祖先糜酶具有高效且特异的血管紧张素II生成活性（转换数约为每秒700次）。因此，血管紧张素II生成活性是糜酶更原始的状态，而这种活性的丧失发生在其中一些丝氨酸蛋白酶进化的后期。
