InterPro domain: IPR033121

General Information

  • Identifier IPR033121
  • Description Peptidase family A1 domain
  • Number of genes 5171
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Abstract

Aspartyl proteases (APs), also known as acid proteases, ([intenz:3.4.23.-]) are a widely distributed family of proteolytic enzymes [ 1 , 2 , 3 , 4 , 5 , 6 ] 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.


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2. The structure and function of the aspartic proteinases. Biochemistry 19, 189-215
3. Structural and evolutionary relationships between retroviral and eucaryotic aspartic proteinases. Essays Biochem. 30, 4663-71
4. Evolutionarily conserved functional mechanics across pepsin-like and retroviral aspartic proteases. Genome Biol Evol 127, 3734-42
5. Extensive expansion of A1 family aspartic proteinases in fungi revealed by evolutionary analyses of 107 complete eukaryotic proteomes. null 6, 1480-94
6. The aspartic proteases. J. Am. Chem. Soc. 210, 5-22

Species distribution

Gene table

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