| Type: | Domain | Name: | Peptidase S54, GlpG peptidase, N-terminal |
| Description: | Proteolytic enzymes that exploit serine in their catalytic activity are ubiquitous, being found in viruses, bacteria and eukaryotes []. 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 []. 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 [].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 []. The geometric orientations of the catalytic residues are similar between families, despite different protein folds []. 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) [, ].This entry represents the N-terminal domain of membrane-bound serine endopeptidases belonging to MEROPS peptidase family S54 (rhomboid-1, clan ST). This domain contains a conserved ASW sequence motif and a single completely conserved residue F that may be functionally important. The tertiary structure of the GlpG protein from Escherichia coli has been determined []. The GlpG protein has six transmembrane domains (other members of the family are predicted to have seven), with the N- and C-terminal ends anchored in the cytoplasm. One transmembrane domain is shorter than the rest, creating an internal, aqueous cavity just below the membrane surface and it is here were proteolysis occurs. There is also a membrane-embedded loop between the first and second transmembrane domains which is postulated to act as a gate controlling substrate access to the active site. No other family of serine peptidases is known to have active site residues within transmembrane domains (although transmembrane active sites are known for aspartic peptidase and metallopeptidases), and the GlpG protein has the type structure for clan ST. | Short Name: | Peptidase_S54_GlpG_N |
