Major Protease Categories
Proteases are divided into four major groups according to the character of their catalytic active site and conditions of action. These groups include: serine proteinases, cysteine (thiol) proteinases, aspartic proteinases, and matrix metalloproteinases (MMPs). Attachment of a protease to a certain group depends on the structure of catalytic site and the amino acid (as one of the constituents) essential for its activity. Proteases are involved in digesting long protein chains into short fragments, splitting the peptide bonds that link amino acid residues. Some of them can detach the terminal amino acids from the protein chain (exopeptidases, such as aminopeptidases, carboxypeptidase A), while others attack internal peptide bonds of a protein (endopeptidases, such as trypsin, chymotrypsin, pepsin, papain and elastase).
Enzymatic Function and Mechanism
Proteases occur in all organisms. These enzymes are involved in a multitude of physiological reactions from simple digestion of food proteins to highly regulated cascades (e.g., the blood-clotting cascade, the complement system, apoptosis pathways, and the invertebrate prophenoloxidase-activating cascade). Proteases can either break specific peptide bonds, depending on the amino acid sequence of a protein, or break down a complete peptide to amino acids. The activity can be a destructive change, abolishing a protein’s function or digesting it to its principal components. It can be an activation of a function, or it can be a signal in a signaling pathway.
Proteases are used throughout an organism for various metabolic processes. Acid proteases secreted into the stomach (such as pepsin) and serine proteases present in duodenum (trypsin and chymotrypsin) enable us to digest the protein in food. Proteases present in blood serum (thrombin, plasmin, Hageman factor, etc.) play an important role in blood-clotting, as well as blood clot lysis, and the correct action of the immune system. Other proteases are present in leukocytes (elastase and cathepsin G) and play several different roles in metabolic control.
Proteases determine the lifetime of other proteins playing an important physiological role like hormones, antibodies, or other enzymes—this is one of the fastest “switching on” and “switching off” regulatory mechanisms in the physiology of an organism. By complex cooperative action the proteases may proceed as cascade reactions, which result in rapid and efficient amplification of an organism’s response to a physiological signal.
Biodiversity of Proteases
Bacteria also secrete proteases to hydrolyze (digest) the peptide bonds in proteins and therefore break the proteins down into their constituent monomers (amino acids). Bacterial and fungal proteases are particularly important to the global carbon and nitrogen cycles in the recycling of proteins, and such activity tends to be regulated by nutritional signals in these organisms. The net impact of nutritional regulation of protease activity among the thousands of species present in soil can be observed at the overall microbial community level as proteins are broken down in response to carbon, nitrogen, or sulfur limitation. A secreted bacterial protease may also act as an exotoxin, and be an example of a virulence factor in bacterial pathogenesis. Bacterial exotoxic proteases destroy extracellular structures. Protease assays are widely used for the investigation of protease inhibitors and the detection of protease activities. Monitoring various protease activities has become a routine task for many biological laboratories. Some proteases have been identified as good drug development targets.