Cathepsins endopeptidases

Gener ally, a family of peptidases contains either exopeptidases or endopeptidases, but there are exceptions. Family Cl contains not only endopeptidases such as cathepsin L, but also the aminopeptidase bleomycin hydrolase. Some members of this family can act as exopeptidases as well as endopeptidases. For example, cathepsin B also acts as a peptidyl-dipeptidase, and... 

Cysteinyl proteases Cathepsins (B, H, K, M, S, T) Proline endopeptidase Interleukin-converting enzyme Apopain (CPP-32)... 

One of the general principles of the Nomenclature Committee is that enzymes should be classified and named according to the reaction they catalyze. However, the overlapping specificities of and great similarities in the action of different peptidases render naming solely on the basis of function impossible [10]. For example, some enzymes can act as both endo- and exopeptidases. Thus, cathepsin H (EC 3.4.22.16) is not only an endopeptidase but also acts as an aminopeptidase (EC 3.4.11), and cathepsin B (EC 3.4.22.1) acts as an endopeptidase as well as a peptidyl-dipeptidase (EC 3.4.15). The actual classification of peptidases is, therefore, a compromise based not only on the reaction catalyzed but also on the chemical nature of the catalytic site, on physiological function, and on historical priority. 

CA 5 Families of mostly endopeptidases (including papain and some cathepsins in family Cl, and calpains in family C2) Gin, Cys, His, Asn/Asp ... 

AA 2 Families of endopeptidases (including pepsin, renin and some cathepsins in family Al) and several other families Asp Two lobes from separate genes... 

This mammalian lysosomal endopeptidase [EC 3.4.22.16] is also known as aleurain, cathepsin B3, cathepsin BA, and benzoylarginineinaphthylamide hydrolase. A member of the peptidase family Cl, the enzyme also acts with an aminopeptidase activity, preferring Arg— Xaa peptide bonds. 

This peptidase family Cl enzyme [EC 3.4.22.15] is an lysosomal endopeptidase with specificity akin to papain. Cathepsin L displays a higher activity toward protein substrates than does cathepsin B. 

Cystcinyi protease Papain CalhepsiL B Cathepsin-Pf Calhepsin-L Calhepsin-M Calhepsin-N Cathepsin-S Calhepsin-T Proiine endopeptidase Interleukin-converting enzyme... 

The cysteinyl proteases include papain calpains I and II cathepsins , H, and L proline endopeptidase and interleukin-converting enzyme (ICE) and its homologs. The most well-studied cysteinyl protease is likely papain, and the first x-ray crystallographic structures of papain [193] and a peptide chloromethylketone inhibitor-papain complex [194] provided the first high resolution molecular maps of the active site. Pioneering studies in the discovery of papain substrate peptide-based inhibitors having P, electrophilic moieties such as aldehydes [195], ketones (e.g., fluoromethylketone, which has been determined [196] to exhibit selectivity for cysteinyl proteases versus serinyl proteases), semicarbazones, and nitriles are noteworthy since 13C-NMR spectro-... 

Substrates for hepatic metabolism include insulin, glucagon, and t-PAs [89,90]. For insulin, an acidic endopeptidase (termed endosomal acidic insulinase ) appears to mediate internalized insulin proteolysis at a number of sites [91]. Specifically, the endosomal activity results from cathepsin D, an aspartic acid protease [92]. Similarly, proteolysis of glucagon has also been attributed to membrane-bound forms ofcathepsins B and D [93]. 

The lysosomal enzymes most relevant to our discussion are the peptidases and the nucleases. The peptidases, also referred to as the cathepsins, comprise at least eight exopeptidases and nine endopeptidases, which between them have a broad range of specificities that enable them to reduce any proteins or peptides to their constituent amino acids. 

Endopeptidases cleave internal peptide bonds and include enkephalinase and cathepsin B. Small peptides are relatively resistant to the action of endopeptidases but their activity is significant for large peptides. 

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... 

A division within the CIA subfamily exists between the papain-like proteases and the cathepsin B-like proteases. Included among the papain-like proteases are cathepsins O, H, L, K and S. Cathepsin O is divergent, whereas the others are more closely related. Among the cathepsin B-like proteases are dipeptidyl-peptidase 1 and the endopeptidases from Giardia. 

The distinction between exopeptidases and endopeptidases is merged for some members of the subfamily CIA. Dipep-tidylpeptidase I acts principally as an exopeptidase, removing N-terminal dipeptides, but may have some endopeptidase activity. Cathepsins B and H both possess endopeptidase activity but also possess exopeptidase activities. Cathepsin B acts as a peptidyl-dipeptidase, releasing C-terminal dipeptides. Cathepsin X is a carboxypeptidase. 

Cathepsin H, which acts as an endopeptidase as well as an aminopeptidase, has been purified from rat liver (9), human liver 12), rat skin 13, 14), and rabbit lung 15, 16). The enzymes from rabbit lung and rat skin have been called a-AT-Bz-Arg-/3-naphthylamide hydrolase, but because of their actions as endoaminopeptidases and their other similarities to the liver enzyme, they may be designated as cathepsins H. Our recent results 40) obtained with antiserum raised in rabbits against rat liver cathepsin H indicate the presence of this enzyme in many organs and tissues of rats. 

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