protease

Proteases, or peptidases, are enzymes that catalyze the hydrolysis of peptide bonds within proteins and peptides. They play essential roles in digestion, protein turnover, activation and inactivation of enzymes and signaling molecules, and various cellular processes. Most proteases are produced as inactive precursors (zymogens) that require proteolytic or chemical activation.

Proteases are commonly classified by their catalytic mechanism: serine proteases (for example trypsin, chymotrypsin); cysteine proteases (papain); metalloproteases (matrix metalloproteinases, MMPs); aspartic proteases (pepsin); and threonine proteases (the proteasome, among others). They can act as endopeptidases, cleaving within a polypeptide, or exopeptidases, trimming terminal residues. Specificity is determined by the active site architecture and substrate-binding pockets.

Most hydrolysis reactions use a catalytic mechanism that involves a nucleophilic attack by an active-site residue (such as serine, cysteine, or aspartate) and a coordinated water molecule. Serine proteases commonly employ a catalytic triad (Ser-His-Asp) that facilitates acyl-enzyme intermediate formation and breakdown. Metalloproteases use a metal ion (often zinc) to polarize a water molecule for nucleophilic attack.

In biology, proteases regulate numerous processes, including digestion, tissue remodeling, immune defense, and maturation of hormones and receptors. Their activity is tightly controlled by zymogen activation, compartmentalization, pH, and endogenous inhibitors such as serpins and canonical inhibitors that bind the active site.

Industrial and medical use of proteases includes digestion of dietary proteins, production of specific peptides, detergent formulations, and proteomics research. Protease inhibitors are important drugs (for example HIV protease inhibitors) and are used to treat diseases where protease activity contributes to pathology.