Human skin fibroblast procollagenase: mechanisms of activation by organomercurials and trypsin

Abstract

Pure human skin fibroblast procollagenase was utilized in this study as a model system in which to examine the pathways of organomercurial and trypsin activation. Three organomercurials, p-(hydroxymercuri)benzoate, mersalyl and p-aminophenylmercuric acetate, were able to fully activate human skin procollagenase with no accompanying loss of MW. Lower MW species were subsequently produced, particularly with a 4th organomercurial, phenylmercuric chloride. The activation process was dependent upon the concentration of the organomercurial compound and the time of incubation, but not on enzyme protein concentration. No evidence of a role for free H was found. Trypsin produced an initial cleavage product of procollagenase which was collagenolytically inactive yet underwent a concentration independent autocatalysis. Thus, procollagenase appeared to have an autocatalytic property which was enhanced by treatment with a variety of agents, all of which may function by perturbation of the zymogen conformation.