Cysteine endopeptidase

Cysteine endopeptidases Clan CD Family Cl 4 ( http //merops.sanger.ac.uk/)... 

Chen JM, Rawlings ND, Stevens RA, Barrett AJ 1998 Identification of the active site of legumain links it to caspases, clostripain and gingipains in a new clan of cysteine endopeptidases. FEBS Lett 441 361-365... 

The NC-IUBMB has introduced a number of changes in the terminology following the proposals made by Barrett, Rawlings and co-workers [7] [8]. The term peptidase should now be used as a synonym for peptide hydrolase and includes all enzymes that hydrolyze peptide bonds. Previously the term peptidases was restricted to exopeptidases . The terms peptidase and protease are now synonymous. For consistency with this nomenclature, the term proteinases has been replaced by endopeptidases . To complete this note on terminology, we remind the reader that the terms cysteine endopeptidases and aspartic endopeptidases were previously called thiol proteinases and acid or carboxyl proteinases , respectively [9],... 

The mechanism of hydrolysis of cysteine peptidases, in particular cysteine endopeptidases (EC 3.4.22), shows similarities and differences with that of serine peptidases [2] [3a] [55 - 59]. Cysteine peptidases also form a covalent, ac-ylated intermediate, but here the attacking nucleophile is the SH group of a cysteine residue, or, rather, the deprotonated thiolate group. Like in serine hydrolases, the imidazole ring of a histidine residue activates the nucleophile, but there is a major difference, since here proton abstraction does not appear to be concerted with nucleophilic substitution but with formation of the stable thiolate-imidazolium ion pair. Presumably as a result of this specific activation of the nucleophile, a H-bond acceptor group like Glu or Asp as found in serine hydrolases is seldom present to complete a catalytic triad. For this reason, cysteine endopeptidases are considered to possess a catalytic dyad (i.e., Cys-S plus H-His+). The active site also contains an oxyanion hole where the terminal NH2 group of a glutamine residue plays a major role. 

Cysteine endopeptidases, like serine endopeptidases, can also catalyze peptide synthesis under preparative conditions [66-68]. Thus, papain has been used to synthesize enkephalins and angiotensin. 

This text is a good source of information on the chemical mechanisms underlying the different modes of peptidase catalysis. Three important enzymes are covered subtilisin, a serine endopepti-dase papain, a cysteine endopeptidase and chymosin, an aspartic endopeptidase. 

Birk serine PIPs (BBPIPs) [137-141] Hordeum (barley) lipid transfer proteins (LTPs) that inhibit malt cysteine endopeptidases [169] and Solanum (potato) Kunitz Pi-type cysteine Pis [185-188] (Table 5). 

Caspases are a family of intracellular cysteine endopeptidases. They play a key role in inflammation and mammalian apoptosis. They are divided into two classes based on the lengths of their N-terminal prodomains. Caspases-1,-2,-4,-5,-8, and -10 have long prodomains and -3,-6,-7,-9 have short prodomains, [from Medical Dictionary Online]... 

Du/tripeptidyl-peptidases Peptidyl-dipeptidases Serine carboxypeptidases MetaUocarboxypeptidases Cysteine carboxypeptidases Omega peptidases Serine endopeptidases Cysteine endopeptidases Aspartic endopeptidases MetaUoendopeptidases Threonine endopeptidases Other endopeptidases... 

Cell mortality of this type appears to be related to the process of apoptosis described in multicellular systems. Apoptosis is mediated by a group of cysteine endopeptidases (EC 3.4.22.x), termed caspases, that cleave after aspartate residues. Thus, caspase activity (or what is better termed caspase-like activity, see Section 2.4.3.2) may prove to be a good marker of this form of cell mortality. 

B. P. O Hara, A. M. Hemmings, D. J. Buttle, and L. H. Pearl. Crystal structure of glycyl endopeptidase from Carica papaya a cysteine endopeptidase of unusual substrate specificity. Biochemistry 34 13190 (1995). 

Cathepsin B (EC 3.4.22.1), a lysosomal cysteine endopeptidase was localised in human alveolar macrophages by the indirect peroxidase-antiperoxidase technique (Burnett et al. 1983). 

Cathepsin B is a lysosomal cysteine endopeptidase with broad specificity for peptide bonds. It preferentially cleaves -Arg-Arg- bonds in small molecule substrates (thus differing from cathepsin L). 

Cysteine endopeptidase Cysteine in the active site Papain, ficin, bromelain, cathepsin B... 

Chicken egg cystatin C consists of one peptide chain with a ca. 120 amino acid residues (Mr 12,700). The two isomers known differ in their isoelectric point (pi 5.6 and pi 6.5) and their immunological properties. This inhibitor inhibits cysteine endopeptidases such as ficin and papain. In fact, cathepsins B, H, and L and dipeptidyl peptidase I are also inhibited. 

The group of cysteine endopeptidases (also called sulfhydryl proteases or thiol proteases) include the higher plant enzymes papain (EC 3.4.22.2) and ficin (EC 3.4.22.3), but also numerous microbial proteolytic enzymes such as Streptococcus cysteine proteinase (EC 3.4.22.10). The enzymes have a rather broad substrate specificity, and specifically recognise aromatic substituents. The specificity is for the second amino acid from the peptide bond to be cleaved. 

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