| Primary Identifier | IPR033874 | Type | Domain |
| Short Name | Memapsin-like |
| description | This entry includes the peptidase domain of aspartic endopeptidases known as memapsins. In humans there are two enzymes, memapsin-1 (also known as BACE2 or beta-site of APP cleaving enzyme 1; MEROPS identifier A01.041) and memapsin-2 (BACE1; MEROPS identifier A01.004).Beta-secretase is an aspartic-acid protease important in the pathogenesis of Alzheimer's disease, and in the formation of myelin sheaths in peripheral nerve cells. It cleaves amyloid precursor protein (APP) to reveal the N terminus of the beta-amyloid peptides. The beta-amyloid peptides are the major components of the amyloid plaques formed in the brain of patients with Alzheimer's disease (AD). Since BACE mediates one of the cleavages responsible for generation of AD, it is regarded as a potential target for pharmacological intervention in AD. Beta-secretase is a member of pepsin family of aspartic proteases (peptidase family A1) [, ].Aspartyl proteases (APs), also known as acid proteases, ([intenz:3.4.23.-]) are a widely distributed family of proteolytic enzymes [, , , , , ]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 andP1' 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. |
