Action of the Metzincin Family

The metzincin catalytic domain consists of a flat surface within a small cleft within which peptide substrates bind and are hydrolyzed (Fig. 8.2a). In astacins, the catalytic domain is stable, but adamalysins require a calcium ion to stabilize the flat surface of the domain above the cleft. Matrilysins require two calcium ions and a second, noncatalytic zinc ion to stabilize this domain (Fig. 8.3). Table 8.3 reviews the roles of specific metal ions that participate in the various stages of collagen processing discussed in this chapter and Chap. 7. 

All human metzincins are secreted as proenzymes. Astacins and adamalysins are mostly activated by calcium-ion-dependent serine proteases pro-protein convertases) that meet up with their substrates in trans-Golgi and secretory vacuoles. These proenzymes are known as furin-like convertases because of their homology to a serine protease called furin and a bacterial endoprotease called subtilisin. The furin-like enzymes require calcium ions to maintain structural stability whereas other serine proteases, represented by trypsin and chymotrypsin, do not. The furin-like pro-protein convertases autocleave their own N-terminal domain propeptide (self-activate) during secretion and then convert the N-terminal domains of co-secreted metzincins. Activation cascades also occur among the 

A similar cascade is associated with inflammation following an injury, infection, or environmental stress (Fig. 8.4). It involves chymotrypsinogen-like serine proteases called 

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