Proteases in cellular regulation minireview series

Proteases form one of the largest and most diverse families of enzymes known. Once considered primarily as "enzymes of digestion," it is now clear that proteases are involved in every aspect of organismal function. All proteases catalyze the addition of water across amide (and ester) bonds to effect cleavage using a reaction involving nucleophilic attack on the carbonyl carbon of the scissile bond. The exact mechanisms of cleavage and active site substituents vary widely among different protease subtypes. This provides the basis for the classification of proteases into the serine proteases, the cysteine proteases, the metalloproteases, etc. More important, however, is the diversity of substrate specificity for different proteases. This involves recognizing internal peptide bonds or those of residues at the NH sub(2) or COOH terminus of the molecule as well as side chains of the surrounding amino acids either amino- or carboxyl-terminal to the bond to be cleaved. It is this great diversity and potential for selectivity that provides the basis for the variety of actions of proteases in different aspects of physiological activity.