Proteases are a diverse group of hydrolytic enzymes, ranging from single-domain catalytic molecules to sophisticated multi-functional macromolecules. Human proteases are divided into five mechanistic classes: aspartate, cysteine, metallo, serine and threonine proteases, based on the catalytic mechanism of hydrolysis. As a protective mechanism against uncontrolled proteolysis, proteases are often produced and secreted as inactive precursors, called zymogens, containing inhibitory N-terminal propeptides. Protease propeptide structures vary considerably in length, ranging from dipeptides and propeptides of about 10 amino acids to complex multifunctional prodomains with hundreds of residues. Interestingly, sequence analysis of the different protease domains has demonstrated that propeptide sequences present higher heterogeneity compared with their catalytic domains. Therefore, we suggest that protease inhibition targeting propeptides might be more specific and have less off-target effects than classical inhibitors. The roles of propeptides, besides keeping protease latency, include correct folding of proteases, compartmentalization, liganding, and functional modulation. Changes in the propeptide sequence, thus, have a tremendous impact on the cognate enzymes. Small modifications of the propeptide sequences modulate the activity of the enzymes, which may be useful as a therapeutic strategy. This review provides an overview of known human proteases, with a focus on the role of their propeptides. We review propeptide functions, activation mechanisms, and possible therapeutic applications.

蛋白酶是多种水解酶，范围从单域催化分子到复杂的多功能大分子。基于水解的催化机理，人蛋白酶分为五类机械类：天冬氨酸，半胱氨酸，金属，丝氨酸和苏氨酸蛋白酶。作为防止不受控制的蛋白水解的保护机制，通常会产生蛋白酶并将其分泌为无活性的前体，称为酶原，其中含有抑制性N端前肽。蛋白酶前肽结构的长度变化很大，范围从约10个氨基酸的二肽和前肽到具有数百个残基的复杂多功能前结构域。有趣的是 对不同蛋白酶结构域的序列分析表明，前肽序列与其催化结构域相比具有更高的异质性。因此，我们建议蛋白酶抑制靶向前肽可能比经典抑制剂更具特异性，脱靶效应更小。除保持蛋白酶潜伏期外，前肽的作用还包括正确折叠蛋白酶，分隔，配体和功能调节。因此，前肽序列的变化对关联酶具有巨大的影响。前肽序列的微小修饰可调节酶的活性，这可用作治疗策略。这篇综述概述了已知的人类蛋白酶，重点是其前肽的作用。我们回顾了前肽的功能，激活机制，