Lysosomal Cysteine Proteases and Their Protein Inhibitors: Recent Developments

Vito Turk* and Boris Turk

Department of Biochemistry and Molecular and Structural Biology, J. Stefan Institute, Sl-1000 Ljubljana, Slovenia
* Corresponding author: E-mail:
+386 1 477 33 65; Fax: +386 1 477 39 84

With the completion of the human genome it has become evident that about 2% of all gene products are proteases, thereby being one of the largest groups of proteins. The general view on proteases as protein degrading enzymes has changed dramatically over the last few years and proteases are now seen as important signalling molecules that are involved in the regulation of numerous vital processes. Cysteine cathepsins occupy a special place as a group of papain-like cysteine proteases that are located predominantly in lysosomes. In addition to their role in intracellular protein turnover, they have essential roles in the immune response, protein processing, bone resorption and a number of other processes. Their activity is strictly regulated, largely through their interaction with their endogenous inhibitors cystatins and thyropins. In this review we discuss the recent status of cysteine cathepsins and their endogenous inhibitors, including their specificity and mechanism of interaction.

Keywords: Cysteine cathepsins, cystatins, protein inhibitors, proteases, structure, mechanism of interaction, drug design