Peptidase clan is the largest group of proteases with common ancestry as identified by structural homology. A peptidase with unknown catalytic type is referred to as an unassigned peptidase clan, which can be classified into 8 peptidase families (U32, U40, U49, U56, U57, U62, U69, and U72). The members of this clan are widely dispersed in diverse microbial pathogens and their apparent involvement in the microbial virulence is not yet known for antibiotic drug discovery. In the present study, we have analyzed their common structural and functional characteristics using evolutionary genetic analysis. As shown by our analysis, the molecular and functional characteristics of this clan diverged across the microbial pathogens. It also indicates that the members of each family might have evolved independently and a peptidase core converged to interconnect the unassigned peptidase clan. Several evolutionary constraints have been identified as selective measures from this clan that inferred on their functional evolution and divergence. Genetic diversity analysis described that many members of this clan have evolved as new molecular functions across the microbial pathogens by imposing the Darwinian positive selection. Structural analysis of this study indicates that members of this clan have a conserved fold, convergence in functional parts, and divergence in spatial structural arrangements. As the results of our study, the neofunctionalization of several unassigned peptidases provides a full virulence for microbial pathogens occupying at the different pathophysiological niche.

通过结构同源性鉴定，肽酶家族是具有共同血统的最大的蛋白酶组。具有未知催化类型的肽酶称为未分配的肽酶家族，其可分为8个肽酶家族（U32，U40，U49，U56，U57，U62，U69和U72）。该氏族的成员广泛散布在各种微生物病原体中，并且其对于微生物毒力的明显参与尚不清楚抗生素药物的发现。在本研究中，我们已经使用进化遗传分析来分析它们的共同结构和功能特征。如我们的分析所示，该氏族的分子和功能特征在微生物病原体之间存在差异。这也表明每个家族的成员可能已经独立进化，并且肽酶核心汇聚在一起以互连未分配的肽酶家族。从该氏族中已经鉴定出几种进化限制作为选择性措施，可以推断其功能进化和分化。遗传多样性分析表明，通过施加达尔文阳性选择，该氏族的许多成员已发展成为跨微生物病原体的新分子功能。这项研究的结构分析表明，该氏族的成员具有保守的折叠，功能部分的融合以及空间结构排列的差异。根据我们的研究结果，