Author/Editor		Cigić, Blaž
Title		Strukturne osnove aktivnosti in inhibicije katepsina C
Translated title		Structural basis of activity and inhibition of cathepsin C
Type		monografija
Place		Ljubljana
Publisher		Medicinska fakulteta
Publication year		1999
Volume		str. 95
Language		slo
Abstract		Cathepsin C is interesting enzyme because of its oligometric structure, long pro-region and specific mechanism of chloride activation. Previously in the shadow of certain other lyposomal proteinases with better defined physiological function, it has recently given rise to a lot of interest. In addition to being involved in protein turnover, it now appears that cathepsin C plays an essential role in the in vivo processing and activation of granzymes A and B, which are required for cytotoxic lymphocyte granule-mediated apoptosis. Involvement in the initiation stage of such an important process requires precise regulation of enzyme activity. Therefore knowledge about the structural characteristics and mechanisms of activation and inhibition is important for understanding the function of the enzyme in the cell. The pro-region of cathepsin C is particular interest, being unusually long and with low sequence similarity to pro-regions of other cysteine proteinases. Recently various authors have shown that mature cathepsin C contains peptides originating from the pro-region. The exact composition of the residual pro-region and mode of interaction with the catalytic part were however not known. We have therefore isolated the constituent chains of cathepsin C and found that a 13.5 kDa N-terminal part of the pro-region remains associated with the mature enzyme, whereas the C-terminal proportion of 10 kDa is cleaved out and lost from the pro-peptide on activation. The residual pro-region is heterogenous, a proportion being cleaved to yield two smaller peptides joined by a disulfide bond. The proportion of cleaved form was found to vary with tissue and enzyme preparation but did not affect the enzyme activity. The pro-region is strongly bound to the rest of enzyme by non-covalent interactions, and is present in equimolar ratio relative to the heavy and light chains which form the catalytic part of the enzyme. (Abstract truncated at 2000 characters).
Descriptors		CATHEPSINS BINDING SITES BINDING, COMPETITIVE CHLORIDES GUANIDINES ENZYME REACTIVATORS ENZYME INHIBITORS