<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>Aspartic endopeptidases <db_xref db="EC" dbkey="3.4.23."/> of vertebrate, fungal and retroviral origin have been characterised [<cite idref="PUB00006548"/>]. More recently, aspartic endopeptidases associated with the processing of bacterial type 4 prepilin [<cite idref="PUB00020023"/>] and archaean preflagellin have been described [<cite idref="PUB00035904"/>, <cite idref="PUB00014343"/>].</p><p>Structurally, aspartic endopeptidases are bilobal enzymes, each lobe contributing a catalytic Asp residue, with an extended active site cleft localised between the two lobes of the molecule. One lobe has probably evolved from the other through a gene duplication event in the distant past. In modern-day enzymes, although the three-dimensional structures are very similar, the amino acid sequences are more divergent, except for the catalytic site motif, which is very conserved. The presence and position of disulphide bridges are other conserved features of aspartic peptidases.All or most aspartate peptidases are endopeptidases. These enzymes have been assigned into clans (proteins which are evolutionary related), and further sub-divided into families, largely on the basis of their tertiary structure.</p><p>This group of aspartic peptidases belongs to the MEROPS family A26 (clan AF). The omptin family, comprises a number of novel outer membrane-associatedserine proteases that are distinct from trypsin-like proteases in that they cleave polypeptides between two basically-charged amino acids [<cite idref="PUB00002071"/>]. The enzyme is sensitive to the serine protease inhibitor diisopropylfluoro-phosphate, to divalent cations such as Cu²⁺, Zn²⁺ and Fe²⁺ [<cite idref="PUB00002071"/>], and istemperature regulated, activity decreasing at lower temperatures [<cite idref="PUB00002071"/>, <cite idref="PUB00002246"/>]. Temperature regulation is most prominently shown in the <taxon tax_id="632">Yersinia pestis</taxon>coagulase/fibrinolysin protein, where coagulase activity is prevalent below 30 degrees Celsius, and fibrinolysin (protease) activity is prevalentabove this point, the optimum temperature being 37 degrees [<cite idref="PUB00003795"/>]. It is possible that this assists in 'flea blockage' and transmission of the bacteria to animals [<cite idref="PUB00003795"/>].</p><p>The <taxon tax_id="562">Escherichia coli</taxon> OmpT has previously been classified as a serine protease with Ser(99) and His(212) as active site residues. The X-ray structure of the enzyme is inconsistent with this classification, and the involvement of a nucleophilic water molecule that is activated by the Asp(210)/His(212) catalytic dyad classifies this as a aspartic endopeptidase where activity is also strongly dependent on Asp(83) and Asp(85). Both may function in binding of the water molecule and/or oxyanion stabilisation. The proposed mechanism implies a novel proteolytic catalytic site [<cite idref="PUB00011706"/>, <cite idref="PUB00011707"/>].</p><p>This entry represents two well conserved regions in the central part of these proteins. </p> Peptidase A26, omptin, conserved site