Cysteine proteinases specificities

Cathepsins are intracellular proteinases that reside within lysosomes or specific intracellular granules. Cathepsins are used to degrade proteins or pqffides that are internalised from the extracellular space. Some cathepsins such as cathepsin-G or cathepsin-K may be released from the cell to degrade specific extracellular matrix proteins. All cathepsins except cathepsin-G (serine) and cathepsin-D (aspartyl) are cysteine proteinases. 

Crystal structure of gingipain R an Arg-specific bacterial cysteine proteinase with a caspase-like fold. EMBOJ. 1999, 18, 5453-5462. 

The proteolytic enzymes are classified into endopeptidases and exopeptidases, according to their site of attack in the substrate molecule. The endopeptidases or proteinases cleave peptide bonds inside peptide chains. They recognize and bind to short sections of the substrate s sequence, and then hydrolyze bonds between particular amino acid residues in a relatively specific way (see p. 94). The proteinases are classified according to their reaction mechanism. In serine proteinases, for example (see C), a serine residue in the enzyme is important for catalysis, while in cysteine proteinases, it is a cysteine residue, and so on. 

Brady, C.P., Brinkworth, R.I., Dalton, J.P., Dowd, A.J., Verity, C.K. and Brindley, P.J. (2000b) Molecular modelling and substrate specificity of discrete cruzipain-like and cathepsinL-like cysteine proteinases of human blood fluke Schistosoma mansoni. Archives in Biochemistry and Biophysics 380, 46-55. 

K6. Kondo, H., Abe, K., Nishimura, I., Watanabe, H., Emori, Y., and Arai, S., Two distinct cystatin species in rice seeds with different specificities against cysteine proteinases. Molecular cloning,... 

O Neill SM, Mills KH, Dalton JP (2001) Fasciola hepatica cathepsin L cysteine proteinase suppresses Bordetella pertussis-specific interferon-gamma production in vivo. Parasite Immunol 23(10) 541-547... 

To date, the latex of Carica papaya L. is known to contain at least four different proteolytic enzymes, namely, papain (E.C. 3.4.22.2), chymopapain (E.C. 3.4.22.6), caricain or papaya proteinase III or 2 (E.C. 3.4.22.30), and glycyl endopeptidase or papaya proteinase IV (E.C. 3.4.22.25). The importance of the latex of the unripe fruit of the tropical tree Carica papaya L. was first noted by G. C. Roy, who in 1873 published in the Calcutta Medical Journal (see Ref. 1) an article entitled The solvent action of papaya juice on the nitrogenous articles of food. The name papain was used for the first time by Wurtz and Bouchet [2] to describe partially purified cysteine proteinases from the papaya latex. They wrote, nous designerons ce ferment sous le nom de papa ine." In 1880, Wurtz postulated that papain acts in fibrin digestion by becoming bound to the fibrin [3]. This is remarkable in that Emil Fisher first described the specific association of enzyme with substrate in 1898. Since that time, many names have been used for commercial latex products, e.g., papayotin, papaoid, etc. 

In 1988, Looze et al. published a series of articles on the cysteine proteinases from papaya latex. In the first article, they described an alternative way to purify chymopapain and papaya proteinase Q to homogeneity [32], In the following articles the primary structures of chymopapain [33] and papaya proteinase 12 [34] were described (Fig. 1). The primary structure of chymopapain determined by Watson et al. [35] is in perfect agreement with the results of Dubois et al. Jacquet et al. described the proteolytic specificities of chymopapain and papaya proteinase 12 [36]. The polypeptide chain of caricain contains 216 amino acid residues (Mr 23283). The molecule shares 148 identical amino acid residues (68.5%) with papain, 141 with chymopapain (65.2%), and 175 with glycyl endo-peptidase (81.0%). The Ai%,280nm is 18.3 [20]. The three-dimensional structure of caricain has been determined by x-ray diffraction analysis [37,38]. 

Szawelski, R. J., and Wharton, C. W. (1981) Kinetic sovent isotope effects on the deacylation og specific acyl-papains. Proton inventory studies on the pap>ain -catalyzed hydrolyses of specific ester substrates analysis of possible transition state structures.Biochem., .Vol. 199, No.3, pp.681-692 Taylor, K(2004) Enzyme Kinetics and Mechanisms, Kluwer AcademicPubhshers, New York Theodorou, L.G., Bieth, J.G. Papamichael, E.M. (2004). Insight Into Catalytic Mechanism of Papain-Like Cysteine Proteinases the case of Di . Applied Biochemistry and Biotechnology-Part A Enzyme Engineering Biotechnology, Vol. 118, No. 1-3, p>p. 171-175, ISSN 0273-2289... 

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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