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The biochemisry of human and parasite cysteine proteases and recent developments in inhibitor-design and their role in physiology and pathology is focused. Papain-like cysteine proteases are expressed as preproenzymes and are synthesized at the rough endoplasmic reticulum.

Research has been conducted on the cathepsin K, responsible for the bone protein matrix degradation. The effect of the cathepsin K inhibitors on the marcomolecular carriers has been investigated and the results are reported.

Research has been conducted on the cathepsins K. The ability of this casepsin to cleave interstitial collagens in their triple helical domains has been investigated via the study of the human casepsin K's S2 pocket engineered into the casepsin L-like subsite and the results are reported.

Research reveals that chimeras of the alpha(sub)1-antitrypsin efficiently inhibit papain-like cysteine protease and that the inhibition is a function of the length of the reactive center loop. Data indicate that the inhibition requires insertion of the reactive center loop into the body of the cysteine protease body.

The mouse SQN-5 serpin inhibits both chymotrypsin-like serine and the papain-like cysteine proteinases through a reactive site loop-dependent inhibitory mechanism. Data indicate that the human and mouse serpin genes seem to have originated from a common ancestor.

A novel protein resembling cathepsin-B and showing about 46% identity to the human tubulointerstitial nephritis antigen (TIN-ag) is isolated and termed as TIN-ag-related protein. The protein detected in vascular smooth muscle cells of various tissues, excepting uterine cells, is a glycosylated secretory protein possessing epidermal growth factor-like domains.

Research has been conducted on the members of the serpine family human squamous cell carcinoma antigens (SCCA) 1 and 2. The SCCA1 inhibition mechanism is described.

Results show that the collagenolytic activity and stability of cathepsin K is determined specifically by chondroitin -4- sulfate (C-4S) present in cartilage. Data also indicate that the cumulative activity of cathepsin K increased by 200 fold in the presence of C-4S.

Research was conducted to examine the functional expression and enzymatic characterization of the novel protease, human cathepsin V, its differences in the electrostatic potential to cathepsin L, its tissue distribution in immune system-related tissues and its chromosomal localization. Results indicate that cathepsin V may likely have an important role to play in thymic self-antigen presentation and may represent a novel target for the treatment of autoimmune disorders.

A study was conducted to test whether the human squamous cell carcinoma antigen 1 (SCCA1) supports inhibitory activity against serine proteinases and whether it can be a potent cross-class inhibitor of the archetypal lysosomal cysteine proteinases cathepsins K, L and S. Reactions were performed in cathepsin buffer at pH 5.5. Results suggested that SCCA1 may be involved in an inhibitory pathway that regulates an array of lysosomal cysteine proteinases.

The open reading frame encoding human bleomycin hydrolase (hBH) consists of 1365 bases and produces a protein with 455 amino acids. The protein is 40% and 89.5% identical to the yeast and rabbit bleomycin hydrolase, respectively. The protein functions as a protease and efficiently degrades bleomycin A2 and B2. Most human organs have low levels of hBH while tumor cell lines have high hBH levels. The high hBH levels are probably responsible for the resistance of tumor cells to bleomycin. The gene produces a 52 kDa protein in Spodoptera frugiperda Sf6 cells that behaves as an aminopeptidase.

Kinetic analysis of mutations of cysteine proteinases residues asparagine 175, tryptophan 177 and tryptophan 181 was conducted using cathepsin S, a naturally occurring variant at position 181 to show the side chain contributions of the residues in catalysis and integration of thiolate-imidazolium ion-pair forms. Asn 175 contributes to ion-pair stability by maintaining a catalysis-inducing conformation. Trp 177 side chains aid in the formation of the S'1 subsite. Trp 177-Trp 181 side chains interaction does not yield any significant effect on ion-pair stability.