Aspartic proteases are a family of eukaryotic protease enzymes that utilize an aspartate residue for catalysis of their peptide substrates. In general, they have two highly-conserved aspartates in the active site and are optimally active at acidic pH. Nearly all known aspartyl proteases are inhibited by pepstatin.

Eukaryotic aspartic proteases include pepsins, cathepsins, and renins. They have a two-domain structure, probably arising from ancestral duplication. Retroviral and retrotransposon proteases are much smaller and appear to be homologous to a single domain of the eukaryotic aspartyl proteases.

Examples

• HIV-1 protease - a major drug-target for treatment of HIV
• Chymosin (or "rennin", with two "n"s)
• Renin (with one "n")
• Cathepsin D
• Pepsin
• Plasmepsin

Mechanism

While a number of different mechanisms for aspartyl proteases have been proposed, the most widely accepted is a general acid-base mechanism involving coordination of a water molecule between the two highly-conserved aspartate residues. One aspartate activates the water by abstracting a proton, enabling the water to attack the carbonyl carbon of the substrate scissile bond, generating a tetrahedral oxyanion intermediate. Rearrangement of this intermediate leads to protonation of the scissile amide.

Subfamilies

• Peptidase A1, beta-site APP cleaving enzyme, BACE

Human proteins containing this domain

External links

References