Proteases are a class of proteins that break down other proteins. They are also called proteolytic enzymes.
Proteases are classified by the amino acids or ligands that catalyze the hydrolysis reaction. For example, serine proteases contain a serine in the active site. The serine is helped by a neighboring histidine and aspartic acid. This combination is called the catalytic triad, and is conserved in all serine proteases. Serine proteases work in a two step fashion; first, they form a covalent bond with the protein to be cleaved; in the second step, water comes in and releases the second half of the cleaved protein. Cysteine proteases use cysteine as a nucleophile just like serine proteases use serine as a nucleophile.
Serine proteases include a number of digestive enzymes, including Trypsin, Chymotrypsin, and Elastase. While they all contain the same three amino acids that work together to catalyze the reaction, called the catalytic triad, they differ in where they cleave proteins. This specificity is due to a binding pocket that contains different functional groups. Chymotrypsin prefers a large hydrophobic residue; its pocket is large and contains hydrophobic residues. In this representation of the binding pocket, the hydrophobic phenylalanine of the substrate is shown in green, and the hydrophobicity of the surrounding amino acids is shown by grey (hydrophobic) or purple (hydrophilic) balls. Trypsin is specific for positively charged residues like lysine, and contains a negative amino acid, aspartic acid, at the bottom of the pocket. Elastase prefers a small neutral residue; it has a very small pocket.
Cysteine proteases include enzymes that have a role in regulating cellular processes such as caspases and deubiquitinase. Caspases hydrolyze proteins during apoptosis. Deubiquitinases play a role in regulating protein degradation, e.g. Cdu1 from Chlamydia.
Another class of protease is aspartate proteases. This family includes HIV protease. HIV produces its proteins as one long chain; HIV protease cleaves the long protein into functional units. Because it cleaves long proteins, it has a tunnel to accommodate the long peptide substrate, and the top "flaps" of the protein can open and closeto allow the substrate in and products out. Aspartate proteases include two aspartate residues in the active site, which increase the reactivity of an active site water molecule to directly cleave the substrate protein.
A third class of proteases are metalloproteases such as carboxypeptidase. Carboxypeptidases remove the C terminal amino acids from proteins. The active site contains zinc , which is bound to the protein through interactions with histidine (H), serine (S) aspartic acid (E) residues.
