Structure-function relationships in class CA1 cysteine peptidase propeptides

Regulation of proteolytic enzyme activity is an essential requirement for cells and tissues because proteolysis at a wrong time and location may be lethal. Proteases are synthesized as inactive or less active precursor molecules in order to prevent such in­appropriate proteolysis. They are activated by limited intra- or intermolecular prote­olysis cleaving off an inhibitory peptide. These regulatory proenzyme regions have at­tracted much attention during the last decade, since it became obvious that they har­bour much more information than just triggering activation. In this review we summarize the structural background of three functions of clan CA1 cysteine peptidase (papain family) proparts, namely the selectivity of their inhibi­tory potency, the participation in correct intracellular targeting and assistance in fold­ing of the mature enzyme. Today, we know more than 500 cysteine peptidases of this family from the plant and animal kingdoms, e.g. papain and the lysosomal cathepsins L and B. As it will be shown, the propeptide functions are determined by certain struc­tural motifs conserved over millions of years of evolution.