Human skin fibroblast procollagenase: mechanisms of activation by organomercurials and trypsin.
Pure human skin fibroblast procollagenase has been 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 molecular weight. Lower molecular weight species were subsequently produced, particularly with a fourth 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 sulfhydryls 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.
D002460:Cell Line; D017364:Collagenases; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism*; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D006902:Hydroxymercuribenzoates / Q000494:pharmacology; D008634:Mersalyl / Q000494:pharmacology; D003012:Microbial Collagenase / Q000378:metabolism*; D008970:Molecular Weight; D009941:Organomercury Compounds / Q000494:pharmacology*; D010662:Phenylmercuric Acetate / Q000031:analogs & derivatives / Q000494:pharmacology; D012867:Skin / Q000201:enzymology*; D014357:Trypsin / Q000378:metabolism*
D004792:Enzyme Precursors; D006902:Hydroxymercuribenzoates; D009941:Organomercury Compounds; C030601:4-hydroxymercuribenzoate; D008634:Mersalyl; C010024:4-aminophenylmercuriacetate; D014357:Trypsin; D017364:Collagenases; C022440:procollagenase; D003012:Microbial Collagenase; D010662:Phenylmercuric Acetate