Proteolytic enzymes that exploit serine in their catalytic activity are ubiquitous, being found in viruses, bacteria and eukaryotes [1]. They include a wide range of peptidase activity, including exopeptidase, endopeptidase, oligopeptidase and omega-peptidase activity. Many families of serine protease have been identified, these being grouped into clans on the basis of structural similarity and other functional evidence [2]. Structures are known for members of the clans and the structures indicate that some appear to be totally unrelated, suggesting different evolutionary origins for the serine peptidases [2].

Not withstanding their different evolutionary origins, there are similarities in the reaction mechanisms of several peptidases. Chymotrypsin, subtilisin and carboxypeptidase C have a catalytic triad of serine, aspartate and histidine in common: serine acts as a nucleophile, aspartate as an electrophile, and histidine as a base [2]. The geometric orientations of the catalytic residues are similar between families, despite different protein folds [2]. The linear arrangements of the catalytic residues commonly reflect clan relationships. For example the catalytic triad in the chymotrypsin clan (PA) is ordered HDS, but is ordered DHS in the subtilisin clan (SB) and SDH in the carboxypeptidase clan (SC) [2, 2].

Limited proteolysis of most large protein precursors is carried out in vivo by the subtilisin-like pro-protein convertases. Many important biological processes such as peptide hormone synthesis, viral protein processing and receptor maturation involve proteolytic processing by these enzymes [3]. The subtilisin-serine protease (SRSP) family hormone and pro-protein convertases (furin, PC1/3, PC2, PC4, PACE4, PC5/6, and PC7/7/LPC) act within the secretory pathway to cleave polypeptide precursors at specific basic sites, generating their biologically active forms. Serum proteins, pro-hormones, receptors, zymogens, viral surface glycoproteins, bacterial toxins, amongst others, are activated by this route [4]. The SRSPs share the same domain structure, including a signal peptide, the pro-peptide, the catalytic domain, the P/middle or homo B domain, and the C terminus.

This entry contains serine endopeptidases belonging to the MEROPS peptidase family S8 (subtilisin family , clan SB).

1. Families of serine peptidases. Meth. Enzymol. 244, 19-61
2. Evolutionary families of peptidases. Biochem. J. 290 ( Pt 1), 205-18
3. Subtilase-like pro-protein convertases: from molecular specificity to therapeutic applications. J. Mol. Endocrinol. 24, 1-22
4. Subtilisin-related serine proteases in the mammalian constitutive secretory pathway. Semin. Cell Dev. Biol. 9, 11-7

Proteolytic enzymes that exploit serine in their catalytic activity are ubiquitous, being found i
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