Thiol Proteinases

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 For consistency with this nomenclature, the term proteinases has been replaced by endopeptidases .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],... 

E. Shaw, R. T. Dean The inhibition of macrophage protein turnover by a selective inhibitor of thiol proteinases. Biochem J 1980, 186, 385-390. 

POMC peptides derived from rat pituitary extracts prolactin-releasing peptides in the bovine hypothalamic extract pseudechetoxin, a peptide blocker of cyclic nucleotide-gated ion channels pseudo-peptide analogues of thiol proteinase inhibitors relaxin-like molecule from the male atlantic stingray, Dasyatis sabina... 

Previous studies have shown that muscle lysosomal hydrolases are released early in the postmortem period due to a decrease in intracellular ATP concentrations. The decreased intracellular ATP level causes the rupture of the lysosomal membrane (14), releasing hydrolytic enzymes (proteases, lipases, and glycosidases) that further potentiate the weakening of membrane integrity and cellular function. Furthermore, as the acidosis increases (due to the anaerobic conditions associated with cellular death) the intramuscular pH to levels reach that which are optimal for the activity of several lysosomal thiol proteinases. 

Milk contains at least two proteinases, plasmin (alkaline milk proteinase) and cathepsin D (acid milk proteinase) and possibly several others, i.e. two thiol proteinases, thrombin and an aminopeptidase. In terms of activity and technological significance, plasmin is the most important of the indigenous proteinases and has been the subject of most attention. The relevant literature has been reviewed by Grufferty and Fox (1988) and Bastian and Brown (1996). 

Asch, H.L. and Dresden, M.H. (1979) Acidic thiol proteinase activity of Schistosoma mansoni egg extracts. Journal of Parasitology 65, 543-549. 

Dresden, M.H., Rutledge, M.L. and Chappell, C.L. (1981) Properties of the acid thiol proteinase from Schistosoma mansoni adults. Molecular Biochemical Parasitology 4, 61-65. 

MA Lawson, BL Semler. Poliovirus thiol proteinase 3C can utilize a serine nucleophile within the putative catalytic triad. Proc Natl Acad Sci (USA) 88 9919-9923, 1991. 

T. Dubois, A. Jacquet, A. O. Schnek, and Y. Looze. Hie thiol proteinases from the latex of Carica papaya L. 1. Fractionation, purification and preliminary characterization, Biol Cheth. Hoppe-Seyier J6P 733 (1988). 

A. Jacquet, T, Kkutschmidt, A. G. Schnek, Y. Looze, and G. Biamrifeer. The thiol proteinases from the latex of Carica papaya L. Ill, Hie primary structure of chymopapain, BioL Chan. Hoppe-Seyier 370 425 (1989). 

B. Ad th and L Polgftr. Transition-state stabilization at thcoxyamon binding sites vt serine and thiol proteinase hydrolyses of thiono and oxygen eaten. Biochemistry 22 117(1983). 

The —CTanion in Ser plays the role of the catalysis so that a-chymotrypsin is a member of the class of enzymes called serine proteinase . We have many serine proteinase such as tripsin, elastase, subtilicin, etc. Papain is called thiol proteinase and contains thiol moiety in place of serine. 

Synonyms cystatin A (R7) Acid cysteine proteinase inhibitor, epidermal SH-proteinase inhibitor, Stefin A cystatin B (R6) neutral cysteine proteinase inhibitor, Stefin B cystatin C See Section 8 in main text cystatin E cystatin M (S10) cystatin F leukocystatin (H2) cystatins S, SA, and SN (12) salivary cysteine proteinase inhibitor cystatin SN cystatin SU (Al) (Grubb, A., unpublished results) LMW- and HMW-kininogens (M9) a-cysteine proteinase inhibitor, a-thiol proteinase inhibitor. 

Double-labeled proteins from rat liver cytosol ( C in long-lived, in short-liv J proteins after in vivo labeling) have been used as substrates for proteinases in vitro. The differences in the degradation rates of short-lived and long-lived proteins in vitro by different proteinases in the presence or absence of different effectors enabled conclusions to be drawn concerning their role in in vivo turnover. The main activity of lysosomal proteinases at pH values of 6.1 and 6.9 was found to be caused by thiol proteinases which decompose short-liv l cytosol proteins preferentially. Autolysis of double-labeled cell fractions showed a remarkably faster breakdown of short-lived substrate proteins only in the soluble part of lysosomes >. 

Many excellent reviews have already been written on the subject of the catalytic centers of serine and thiol proteinases (e.g.. Kraut, 1977 Baker and Drenth, 1987 Warshel etai, 1989). In this paper the focus is specifically on the structure of the catalytic triad in lipases, with emphasis on the differences from and similarities to the catalytic centers of proteinases. The atomic coordinates for the G. candidum lipase were not available when this review was written, and the analysis of the stereochemistry of the active centers is therefore restricted to lipases from R. miehei and the human pancreas. 

Various cyclopropenones exhibit biological activity. For example, hydroxymethylcyclo-propenone is known as an antibiotic, called pentricin, and some cyclopropenones act as thiol proteinase inhibitors ... 

Murzin, A.G. (1993). Sweet-tasting protein monellin is related to the cystatin family of thiol proteinase inhibitors. J. Mol. Biol. 230, 689-694. 

Reed, S., Keene, W. E. and McKerrow, J. H. (1989) Thiol proteinase expression correlates with pathogenicity of Entamoeba histolytica. J. Clin. Microbiol. 21 2772-2777. 

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