Procollagen Peptidase: An Enzyme Excising the Coordination Peptides of Procollagen

Abstract

A heritable connective tissue disorder of cattle, dermatosparaxis, is characterized by an extreme fragility of the skin and the presence of additional peptides at the N-terminal extremities of the collagen alpha chains, p-alpha(1) and p-alpha(2). The existence of an enzyme activity is demonstrated in normal connective tissues that is capable of cleaving these additional N-terminal peptides from dermatosparaxic collagen. The activity is demonstratable with dermatosparaxic collagen in solution, as well as with reconstituted dermatosparaxic collagen fibrils polymerized in vitro. It has a pH optimum of about 7.0 and is inhibited by EDTA and mercaptoethanol. Differences in K(m) and V(max) values exist depending on the substrate utilized, i.e., p-alpha(1) or p-alpha(2); and the presence of additional amounts of one substrate, p-alpha(1), alters the concentration requirement for the second substrate, p-alpha(2). The product of the excision reaction with p-alpha(1) as substrate is an equimolar amount of normal alpha(1) monomer; the product when p-alpha(2) is substrate is an equimolar amount of normal alpha(2) monomer. The enzyme is present in normal calf skin, tendon, aorta, cartilage, and lung; it can be demonstrated in the skin of rats and humans. The enzyme activity is absent in dermatosparaxic connective tissues, thus suggesting that dermatosparaxis is caused by the absence of a normal enzyme function rather than by the production of an abnormal collagen.