<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>Cysteine peptidases have characteristic molecular topologies, which can be seen not only in their three-dimensional structures, but commonly also in the two-dimensional structures. These are peptidases in which the nucleophile is the sulphydryl group of a cysteine residue. Cysteine proteases are divided into clans (proteins which are evolutionary related), and further sub-divided into families, on the basis of the architecture of their catalytic dyad or triad [<cite idref="PUB00011704"/>]. </p><p>This group of cysteine peptidases belong to MEROPS peptidase family C15 (pyroglutamyl peptidase I, clan CF). The type example being pyroglutamyl peptidase I of <taxon tax_id="1390">Bacillus amyloliquefaciens</taxon>. </p><p>Pyroglutamyl/pyrrolidone carboxyl peptidase (Pcp or PYRase) is an exopeptidase thathydrolytically removes the pGlu from pGlu-peptides or pGlu-proteins [<cite idref="PUB00004992"/>, <cite idref="PUB00001639"/>].PYRase has been found in prokaryotes and eukaryotes where at least two different classes have been characterised: the firstcontaining bacterial and animal type I PYRases, and the second containinganimal type II and serum PYRases. Type I and bacterial PYRases are solubleenzymes, while type II PYRases are membrane-bound. The primary applicationof PYRase has been its utilisation for protein or peptide sequencing, andbacterial diagnosis [<cite idref="PUB00001639"/>]. The conserved residues Cys-144 and His-168 havebeen identified by inhibition and mutagenesis studies [<cite idref="PUB00004992"/>, <cite idref="PUB00002244"/>].</p> Peptidase C15, pyroglutamyl peptidase I