Kallikreins in Humans and Other Species

residue (cysteine proteases), aspartate (aspartate proteases), metal ion (metalloproteases) or serine (serine proteases). Serine proteases are a family of enzymes that utilizes a uniquely activated serine residue in the substrate-binding site to catalytically hydrolyze peptide bonds (Schultz and Liebman, 1997). This active site is characterized by the irreversible interaction with diisopropylfluorophosphate (DFP). Of all the serines in the protein, DFP can only react with the active serine to form a phosphate ester (Schultz and Liebman, 1997). Out of the estimated 400 – 500 proteases in the human genome, 32% are predicted to be serine proteases (Southan, 2001). This large family includes the digestive enzymes (e.g., trypsin, chymotrtypsin), the kringle domain-containing growth factors (e.g., tissue plasminogen activator), some of the blood clotting factors and the kallikreins. Serine proteases are involved in many vital functions such as digestion, coagulation and fibrinolysis, tissue remodelling, activation of hormones, growth factors and in extracellular matrix protein degradation. A number of serine proteases are secreted as inactive ‘zymogens’, which require limited proteolysis to release the active enzyme. Others are anchored to the cell membrane.