Cathepsin catalytic mechanism

Cysteine proteases are so called because of a critical cysteine involved (together with an adjacent histidine) in the catalytic mechanism. Cysteine proteases include papain-related proteases, calpain-related proteases and the caspases. Papain-like cysteine proteases include the plant enzymes actinidin, aleurain, bromelain, caricain, chymopapain, ficin and papain and the lysosomal cathepsins B, C, H, K, L and S. Cathepsin C is multimeric (MW -200,000), but the other papain-related proteases are monomeric with MWs of about 20,000-35,000. While cathepsin C is a dipeptidyl aminopeptidase, the other enzymes are endopeptidases. Cathepsin B is an endopeptidase and a dipeptidyl carboxypeptidase. Cathepsin H is an endopeptidase and an aminopeptidase. In higher animals, cathepsin B generates peptides from antigens for presentation to T cells by the major histocompatibility... 

The reaction conditions can be optimized by examining the effect of different factors snch as water content, temperature, pH, surfactant concentration, reaction time, or product yield. Proteases are classified according to their catalytic mechanisms. Four mechanistic classes have been recognized by the International Union of Biochemistry and Molecular Biology serine proteases (chymotrypsin, trypsin, elastase, subtilisin), cysteine proteases (papain, cathepsins, caspases), aspartic proteases (pepsins, cathepsins, lennins), and metallo proteases. 

The carboxyl proteases are so called because they have two catalytically essential aspartate residues. They were formerly called acid proteases because most of them are active at low pH. The best-known member of the family is pepsin, which has the distinction of being the first enzyme to be named (in 1825, by T. Schwann). Other members are chymosin (rennin) cathepsin D Rhizopus-pepsin (from Rhizopus chinensis) penicillinopepsin (from Penicillium janthinel-lum) the enzyme from Endothia parasitica and renin, which is involved in the regulation of blood pressure. These constitute a homologous family, and all have an Mr of about 35 000. The aspartyl proteases have been thrown into prominence by the discovery of a retroviral subfamily, including one from HIV that is the target of therapy for AIDS. These are homodimers of subunits of about 100 residues.156,157 All the aspartyl proteases contain the two essential aspartyl residues. Their reaction mechanism is the most obscure of all the proteases, and there are no simple chemical models for guidance. 

Effector caspases are activated by a transactivation mechanism, which is characterized by the catalytic action of a mature caspase on a procaspase (Thornberry et al., 1997 Earnshaw et al., 1999 Slee et al., 1999). Nevertheless, their activation can also occur by the action of other proteases. Granzyme B, a serine-protease, also has proteolytic specificity for aspartic acid residues. It is able to cleave and directly activate caspase 3 (Darmon et al., 1995). Cathepsin B, a lysosomal protease, cleaves and activates procaspase 11 (Schotte et al., 1998). 

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