InterPro domain: IPR008758

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 ].

This group of serine peptidases belong to MEROPS peptidase family S28 (clan SC). The predicted active site residues for members of this family and family S10 occur in the same order in the sequence: S, D, H.

These serine proteases include several eukaryotic enzymes such as lysosomal Pro-X carboxypeptidase, dipeptidyl-peptidase II, and thymus-specific serine peptidase [ 3 , 4 , 5 , 6 ].

1. Families of serine peptidases. Meth. Enzymol. 244, 19-61
2. Evolutionary families of peptidases. Biochem. J. 290 ( Pt 1), 205-18
3. Cloning of a novel MHC-encoded serine peptidase highly expressed by cortical epithelial cells of the thymus. Cell. Immunol. 196, 80-6
4. Chromosomal localization of two mouse genes encoding thymus-specific serine peptidase and thymus-expressed acidic protein. Immunogenetics 51, 984-6
5. Cloning and functional expression of rat kidney dipeptidyl peptidase II. Biochem. J. 353, 283-90
6. Purification, molecular cloning, and immunohistochemical localization of dipeptidyl peptidase II from the rat kidney and its identity with quiescent cell proline dipeptidase. J. Biochem. 129, 279-88