Papain-like cysteine proteases are processive and digestive enzymes. Failure in biological control mechanisms causes a wide range of diseases, including several genetic disorders. Most of these enzymes are endopeptidases, although some exhibit an exopeptidase activity. There are 11 human enzymes known and among them 9 with known crystal structures. The enzyme activities are regulated by their propeptides and/or protein inhibitors cystatins and thyropins. Recent findings confirm the role of lysosomal cathepsins in two important mechanisms, antigen processing and apoptosis. Namely, a) the important role of cathepsins S and L in antigen processing via MHC-class II molecules was found and b) there is increasing evidence that lysosomal cathepsins are actively involved in apoptosis by the cleavage of a proapoptotic Bcl-2 family member Bid. In conclusion, cathepsins represent a challenge for further investigations, including drug-design.
*Kolokvij Instituta Ruđer Bošković