<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>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 [<cite idref="PUB00035098"/>]. 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 [<cite idref="PUB00035099"/>]. 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.</p><p>This group of serine peptidases belong to the MEROPS peptidase family S8 (subtilisin family, clan SB). Members of this particular family have not been assigned to one of the S8 subfamilies.</p> <p>Pathogenic bacteria produce a number of virulence factors to facilitatehost infection, and to combat competing species. Antibiotics are secreted by some pathogenic prokaryotes to lyse cells, some of which have been adapted by humans for use against virulent microbes. Amongst these are the lantibiotics, produced exclusively by Gram-positive bacteria. Lantibiotics are small, heavily post-translationally modified peptides that inhibit rival cell growth and are strongly cationic. </p><p>Lantibiotic genes reside on the bacterial chromosome, where they cluster with genes that adapt and secrete them to the extracellular space. Many of these so-called 'pathogenicity islands' have been characterised, including the epidermin (epi) cluster in Staphylococcus epidermis, and the nisin (nis) cluster in <taxon tax_id="1358">Lactococcus lactis</taxon> [<cite idref="PUB00011677"/>]. The gene encoding the lantibiotic is flanked by 3 regulatory genes: 2 that are usually involved ina 2-component regulatory system, and another that cleaves the signal peptidefrom the precursor to produce the mature lantibiotic.</p><p>This protein (usually designated with a "P" suffix - nisP, mutP, etc.) is highly conserved amongst pathogenic species, and is essential for virulence and survival of the bacterium against competitors in the host [<cite idref="PUB00011677"/>]. Recently,a novel pathogenicity island in resistant <taxon tax_id="1351">Enterococcus faecalis</taxon> was sequenced. In addition to the lantibiotic Cyl gene cluster, this revealed a novel set of virulence factors involved in vancomycin resistance and pathogenicity [<cite idref="PUB00011678"/>]. </p> Peptidase S8, lantibiotic leader peptide processing protein