Pathways & interactions
Plasmepsin 5 (IPR033866)
Short name: Plasmepsin_5
Overlapping homologous superfamilies
- Aspartic peptidase domain superfamily (IPR021109)
- Peptidase family A1 domain (IPR033121)
- Plasmepsin 5 (IPR033866)
The entry contains a group of aspartic proteinases homologous to plasmepsin 5 (MEROPS identifier A01.075). Plasmepsins are a class of at least 10 enzymes produced by the Plasmodium parasite. Because some plasmepsins degrade haemoglobin, they are an important cause of symptoms in malaria sufferers. This family of enzymes is a potential target for anti-malarial drugs. There are several types of plasmepsins, closely related but varying in the specificity of cleavage site. The name plasmepsin may come from plasmodium (the organism) and pepsin (a common aspartic acid protease with similar molecular structure). This group of aspartate endopeptidases is classified by MEROPS as the peptidase family A1 (pepsin A, clan AA).
Proteins exported by Plasmodium to its host erythrocyte contain a signal peptide followed by a transit PEXEL motif (Arg-Xaa-Leu-Xaa-Glu/Gln/Asp). Plasmepsin 5 removes the PEXEL motif [PMID: 20130644]. Cleavage occurs at the leucyl bond [PMID: 21342099]. Some proteins lacking the canonical PEXEL motif are also processed, but not if Lys occupies P3 or Ile is in P1 [PMID: 23387285].
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.
- cd06096 (Plasmepsin_5)