Kunitz-type domains are ubiquitously found in natural systems as serine protease inhibitors or animal toxins in venomous animals. Kunitz motif is a cysteine-rich peptide chain of ~ 60 amino acid residues with alpha and beta fold, stabilized by three conserved disulfide bridges. An extensive dataset of amino acid variations is found on sequence analysis of various Kunitz peptides. Kunitz peptides show diverse biological activities like inhibition of proteases of other classes and/or adopting a new function of blocking or modulating the ion channels. Based on the amino acid residues at the functional site of various Kunitz-type inhibitors, it is inferred that this ‘flexibility within the structural rigidity’ is responsible for multiple biological activities. Accelerated evolution of functional sites in response to the co-evolving molecular targets of the hosts of venomous animals or parasites, gene sharing, and gene duplication have been discussed as the most likely mechanisms responsible for the functional heterogeneity of Kunitz-domain inhibitors.

Kunitz型结构域在天然系统中作为丝氨酸蛋白酶抑制剂或有毒动物中的动物毒素普遍存在。Kunitz基序是一条富含半胱氨酸的肽链，具有约60个氨基酸残基，具有α和β折叠，并通过三个保守的二硫键稳定。在各种Kunitz肽的序列分析中发现了广泛的氨基酸变异数据集。Kunitz肽具有多种生物学活性，例如抑制其他种类的蛋白酶和/或具有阻断或调节离子通道的新功能。根据各种Kunitz型抑制剂功能位点的氨基酸残基，可以推断这种“结构刚性内的柔性”负责多种生物活性。