Abstract
Background:
Proteases are enzymes that break down proteins, and serine proteases are an important subset of these enzymes. Prolyl oligopeptidase (POP) is a family of serine proteases that has ability to cleave peptide bonds involving proline residues and it is unique for its ability to cleave various small oligopeptides shorter than 30 amino acids. The S9 family from MEROPS database, which includes POP, is classified into four subcategories based on active site motifs. These protease subfamilies assume a crucial position owing to their diverse biological roles and potential therapeutic applications in various diseases.
Results:
In this study, we have examined ~32000 completely annotated bacterial genomes from the NCBI RefSeq Assembly database using computational techniques to identify annotated S9 family proteins. This results in the discovery of 61,660 bacterial genes that contain domains and sequence signatures of S9 family members (referred to as POP homologues). We have classified these sequences into distinct subfamilies through machine learning approaches and conducted a comprehensive analysis of their distribution across various phyla and species. We notice significant enrichment of POP homologues in distinct phyla and species.
All bacterial phyla showed diverse domain architecture in genes containing S9 family domains.
Distinct subclusters and class-specific motifs were identified, using phylogeny and motif-finding, suggesting difference in substrate specificity in POP homologues.
Conclusions:
We present a comprehensive study presenting the distribution, classification and domain architecture of S9 family proteins. In addition, our study also demonstrate that, despite belonging to same subfamily (S9A), POPs can be different in their substrate and substrate binding capabilities. This can enable future research of these gene families that are involved in many important biological processes.