Proteinases

Proteinases, also called proteases, are enzymes that catalyze the hydrolysis of peptide bonds in proteins. They play essential roles in digestion, protein turnover, immune defense, and tissue remodeling, functioning in various cellular compartments from lysosomes to the extracellular space. Proteinases are categorized by their catalytic mechanisms into serine proteases, cysteine proteases, aspartic proteases, metalloproteases, and threonine proteases, among others. Many proteases are secreted as inactive zymogens and require proteolytic activation to become active.

Serine proteases use a catalytic triad of serine, histidine, and aspartate to generate a nucleophilic attack on the peptide bond. Cysteine proteases rely on a cysteine thiolate, while metalloproteases coordinate a metal ion, typically zinc, to activate water for hydrolysis. Aspartic proteases employ two aspartates in the active site, and threonine proteases (such as the proteasome) use the N-terminal threonine as the nucleophile. Substrate specificity varies, with some proteases cleaving after specific amino acids or motifs; others act on internal bonds (endopeptidases) or trim terminal residues (exopeptidases).

Physiological roles include digestive enzymes (pepsin, trypsin, chymotrypsin), immune proteases (granzymes), and extracellular matrix remodeling by matrix metalloproteinases. Intracellular proteolysis by the proteasome is essential for protein quality control. Regulation occurs through zymogen activation, compartmentalization, pH, and inhibitors such as serpins, cystatins, and TIMPs. Aberrant protease activity is linked to diseases including cancer, arthritis, pancreatitis, and neurodegeneration. Protease inhibitors have therapeutic uses, and proteases are employed in industrial applications such as detergents and food processing.