Peptidase S9, prolyl oligopeptidase, catalytic domain
<p>In the MEROPS database peptidases and peptidase homologues are grouped into clans and families. Clans are groups of families for which there is evidence of common ancestry based on a common structural fold:</p><ul> <li>Each clan is identified with two letters, the first representing the catalytic type of the families included in the clan (with the letter 'P' being used for a clan containing families of more than one of the catalytic types serine, threonine and cysteine). Some families cannot yet be assigned to clans, and when a formal assignment is required, such a family is described as belonging to clan A-, C-, M-, N-, S-, T- or U-, according to the catalytic type. Some clans are divided into subclans because there is evidence of a very ancient divergence within the clan, for example MA(E), the gluzincins, and MA(M), the metzincins.</li><li>Peptidase families are grouped by their catalytic type, the first character representing the catalytic type: A, aspartic; C, cysteine; G, glutamic acid; M, metallo; N, asparagine; S, serine; T, threonine; and U, unknown. The serine, threonine and cysteine peptidases utilise the amino acid as a nucleophile and form an acyl intermediate - these peptidases can also readily act as transferases. In the case of aspartic, glutamic and metallopeptidases, the nucleophile is an activated water molecule. In the case of the asparagine endopeptidases, the nucleophile is asparagine and all are self-processing endopeptidases. </li></ul><p>In many instances the structural protein fold that characterises the clan or family may have lost its catalytic activity, yet retain its function in protein recognition and binding. </p><p>Proteolytic enzymes that exploit serine in their catalytic activity are ubiquitous, being found in viruses, bacteria and eukaryotes [<cite idref="PUB00003576"/>]. They include a wide range of peptidase activity, including exopeptidase, endopeptidase, oligopeptidase and omega-peptidase activity. Over 20 families (denoted S1 - S66) of serine protease have been identified, these being grouped into clans on the basis of structural similarity and other functional evidence [<cite idref="PUB00003576"/>]. 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 [<cite idref="PUB00003576"/>].</p><p>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 [<cite idref="PUB00003576"/>]. The geometric orientations of the catalytic residues are similar between families, despite different protein folds [<cite idref="PUB00003576"/>]. 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) [<cite idref="PUB00003576"/>, <cite idref="PUB00000522"/>].</p><p>This domain covers the active site serine of the serine peptidases belonging to MEROPS peptidase family S9 (prolyl oligopeptidase family, clan SC). The protein fold of the peptidase domain for members of this family resembles that of serine carboxypeptidase D, the type example of clan SC. Examples of protein families containing this domain are:</p><p> <ul><li>Prolyl endopeptidase (<db_xref db="EC" dbkey="3.4.21.26"/>) (PE) (also called post-proline cleaving enzyme). PE is an enzyme that cleaves peptide bonds on the C-terminal side of prolyl residues. The sequence of PE has been obtained from a mammalian species (pig) and from bacteria (<taxon tax_id="238">Flavobacterium meningosepticum</taxon> and <taxon tax_id="644">Aeromonas hydrophila</taxon>); there is a high degree of sequence conservation between these sequences.</li> <li> <taxon tax_id="562">Escherichia coli</taxon> protease II (<db_xref db="EC" dbkey="3.4.21.83"/>) (oligopeptidase B) (gene prtB) which cleaves peptide bonds on the C-terminal side of lysyl and argininyl residues.</li> <li>Dipeptidyl peptidase IV (<db_xref db="EC" dbkey="3.4.14.5"/>) (DPP IV). DPP IV is an enzyme that removes N-terminal dipeptides sequentially from polypeptides having unsubstituted N-termini provided that the penultimate residue is proline.</li> <li> <taxon tax_id="4932">Saccharomyces cerevisiae</taxon> (Baker's yeast) vacuolar dipeptidyl aminopeptidases A and B (DPAP A and DPAP B), encoded by the STE13 and DAP2 genes respectively. DPAP A is responsible for the proteolytic maturation of the alpha-factor precursor.</li> <li>Acylamino-acid-releasing enzyme (<db_xref db="EC" dbkey="3.4.19.1"/>) (acyl-peptide hydrolase). This enzyme catalyses the hydrolysis of the amino-terminal peptide bond of an N-acetylated protein to generate a N-acetylated amino acid and a protein with a free amino-terminus.</li> </ul> </p><p>These proteins belong to MEROPS peptidase families S9A, S9B and S9C.</p>