Oligopeptidase
New experimental evidences showed that, under physiological conditions, non-lysosomal proteases were responsible for limited proteolysis of intra- and/or extracellular proteins, a concept originally conceived by Linderstᴓm-Lang in 1950.
[3] Endogenous or exogenous proteins are processed by non-lysosomal proteases into intermediate-sized polypeptides, which display gene and metabolic regulation, neurologic, endocrine, and immunological roles, whose dysfunction might explain a number of pathologies.
Short 'oligopeptides', predominantly smaller than 30 amino acids in length, play essential roles as hormones, in the surveillance against pathogens, and in neurological activities.
Oligopeptidase is a term coined in 1979 to designate a sub-group of the endopeptidases,[8][13] which are not involved in the digestion nor in the processing of proteins like the pancreatic enzymes, proteasomes, cathepsins among many others.
The peptide has first to penetrate into a 4 Å hole on the surface of the enzyme in order to reach an 8,500Å3 internal cavity, where the active site is located.
[15][16] This contrasts with the classical specificity of proteolytic enzymes, which derives from the chemical features of the amino acid side chains around the scissile bond.
[16][28] TOP, a ubiquitous cytosolic oligopeptidase, is a remarkable example of how this enzyme could play an essential role in immune defense against cancer cells.
[31] The involvement of peptides in cell-cell interactions and in neuropsychiatric, autoimmune, and neurovegetative diseases are waiting for peptidomics[32] and gene silencing approaches, which will expedite the formation of new concepts in an emerging era for oligopeptidases.
The ACE has benefited the most from a thorough knowledge on the enzyme structure and its mechanism of catalysis leading to the better understanding of its role in cardiovascular pathologies and therapeutics.
Accordingly, for over 30 years, the treatment of human arterial hypertension has taken advantage of ACE inhibition by active site-directed inhibitors like captopril, enalapril, lisinopril, and others.
