Proteases, also known as proteolytic enzymes, are enzymes that catalyze the breakdown of proteins by hydrolysis of peptide bonds. By cleaving proteins, proteases are involved in the control of a large number of key physiological processes such as cell-cycle progression, cell proliferation and cell death, DNA replication, tissue remodeling, haemostasis (coagulation), wound healing and the immune response. So far, inappropriate proteolysis has been found to have a major role in cancer as well as cardiovascular, inflammatory, neurodegenerative, bacterial, viral and parasitic diseases. Because excessive proteolysis can be prevented by blocking the appropriate proteases, this area is widely explored by pharmaceutical companies. Their mechanism of action classifies the large family of proteases as either serine, cysteine or threonine proteases (amino-terminal nucleophile hydrolases), or as aspartic, metallo and glutamic proteases (with glutamic proteases being the only subtype not found in mammals so far). Interestingly, the serine and cysteine proteases act directly as nucleophiles to attack the substrate (by generating covalent acyl enzyme intermediates). On the other hand, the aspartyl and zinc proteases activate water molecules as the direct attacking species on the peptide bond. Proteases of the different classes can be further grouped into families on the basis of amino acid sequence comparison, and families can be assembled into clans based on similarities in their three-dimensional structures.
A class of aminopeptidases, widely distributed throughout the animal and plant kingdoms, and found in many subcellular organelles, in cytoplasm, and as membrane components. The aminopeptidase MetAP2 (EC 18.104.22.168) is of particular interest because the enzyme plays a key role in angiogenesis, the growth of new blood vessels, which is necessary for the progression of diseases including solid tumor cancers and rheumatoid arthritis.
 Targeting proteases: successes, failures and future prospects. Boris Turk. Nature Reviews – Drug Discovery. Volume 5, 2006, 785-799.
 Proteases: Multifunctional Enzymes in Life and Disease. C. López-Otín, J.S. Bond. J. Biol. Chem. 2008, 283, 30433-30437.
 Methionine aminopeptidase 2 inhibition is an effective treatment strategy for neuroblastoma in preclinical models. M.J. Morowitz et al. Clin. Cancer Res. 2005, 11, 2680-2685.