Aspartate Protease & Regulator-enzyme

Aspartic proteases are a group of protease enzymes that use two highly conserved aspartic acid residues in the active site for catalytic cleavage of their peptide substrates. Unlike serine or cysteine proteases these proteases do not form a covalent intermediate during cleavage. Nearly all known aspartyl proteases are inhibited by pepstatin. HIV protease is unusual in that it is a homodimer and each of the monomeric units contribute an aspartic acid.

As the smallest class, aspartic proteases nevertheless play an important role in health and disease. For example, beta-secretase are the two enzymes necessary to release A beta peptides from the Alzheimer's precursor protein. BACE1 and Cathepsin D & E all have beta secretase activity and Presenilin is the catalytic subunit of the gamma secretase complex that contains three other integral membrane proteins. As a general protease inhibitor, alpha 2-Macroglobulin is able to inhibit all four classes of proteases by a unique trapping mechanism.