Aspergillopepsin-like catalytic domain (IPR034163)

Short name: Aspergillopepsin-like_cat_dom

Overlapping homologous superfamilies

Domain relationships


This entry represents the peptidase domain found in a group of aspartic endopeptidases of fungal origin, including aspergillopepsin (MEROPS ientifier A01.016) [PMID: 11418762], rhizopuspepsin (A01.012), endothiapepsin (A01.017) and penicillopepsin (A01.011) [PMID: 339694]. Aspergillopepsin from A. fumigatus is involved in invasive aspergillosis owing to its elastolytic activity [PMID: 16940951] and aspergillopepsins from the mold A. saitoi are used in the fermentation industry [PMID: 21699]. The members in this entry have an optimal acidic pH (5.5) and cleave protein substrates with similar specificity to that of porcine pepsin A, preferring hydrophobic residues at P1 and P1' in the cleavage site. This group of aspartate proteases is classified by MEROPS as the peptidase family A1 (pepsin A, clan AA) [PMID: 7674916].

Aspartyl proteases (APs), also known as acid proteases, (EC:3.4.23.-) are a widely distributed family of proteolytic enzymes [PMID: 6795036, PMID: 2194475, PMID: 1851433, PMID: 15771507, PMID: 24869856, PMID: 1455179] known to exist in vertebrates, fungi, plants, retroviruses and some plant viruses. APs use an Asp dyad to hydrolyze peptide bonds.

APs found in eukaryotic cells are alpha/beta monomers composed of two asymmetric lobes ("bilobed"). Each of the lobes provides a catalytic Asp residue, positioned within the hallmark motif Asp-Thr/Ser-Gly, to the active site. The N- and C-terminal domains, although structurally related by a 2-fold axis, have only limited sequence homology except the vicinity of the active site. This suggests that the enzymes evolved by an ancient duplication event. The enzymes specifically cleave bonds in peptides which have at least six residues in length with hydrophobic residues in both the P1 and P1' positions. The active site is located at the groove formed by the two lobes, with an extended loop projecting over the cleft to form an 11-residue flap, which encloses substrates and inhibitors in the active site. Specificity is determined by nearest-neighbour hydrophobic residues surrounding the catalytic aspartates, and by three residues in the flap. The enzymes are mostly secreted from cells as inactive proenzymes that activate autocatalytically at acidic pH. Eukaryotic APs form peptidase family A1 of clan AA.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.