Proteases are widely found in organisms participating in the decomposition of proteins to maintain the organisms' normal life activities. Protease inhibitors regulate the activities of target proteases by binding to their active sites, thereby affecting protein metabolism. The key amino acid mutations in proteases and protease inhibitors can affect their physiological functions, stability, catalytic activity, and inhibition specificity. More active, stable, specific, environmentally friendly and cheap proteases and protease inhibitors might be obtained by excavating various natural mutants of proteases and protease inhibitors, analyzing their key active sites by using protein engineering methods. Here, we review the studies on proteases' key active sites and protease inhibitors to deepen the understanding of the active mechanism of proteases and their inhibitors.
蛋白酶广泛存在于生物体中，参与分解蛋白质，维持生物体正常的生命活动。蛋白酶抑制剂通过与蛋白酶活性位点结合调控靶蛋白酶活性，从而影响蛋白质代谢。蛋白酶及其抑制剂关键氨基酸的突变，可以影响其生理功能、稳定性、催化活性、抑制特异性等。通过挖掘自然界蛋白酶及其抑制剂的各种突变体，分析它们的关键活性位点，并运用蛋白质工程手段改造和设计活性更强、稳定性更高、特异性更好、环境更友好、成本更低的蛋白酶及其抑制剂，已成为当前的热点研究之一。文中对近年来蛋白酶及其抑制剂关键活性位点研究进行了简要综述，以期深化人们对蛋白酶及其抑制剂活性作用机制的认识，并为蛋白酶及其抑制剂的生物学活性改造研究提供理论参考。.
Keywords: activity modification; key active site; physiological function; protease; protease inhibitor.