ENHANCEMENT OF FIBRIN BINDING AND ACTIVATION OF PLASMINOGEN BY STAPLABIN THROUGH INDUCTION OF A CONFORMATIONAL CHANGE IN PLASMINOGEN

Staplabin (0.3-0.6 mM), a fungal triprenyl phenol, enhanced 3-6-fold t he plasminogen activator-catalyzed activation of Glu-plasminogen and L ys-plasminogen as well as their binding to fibrin, Staplabin was not s timulatory to the amidolytic activity of plasmin and plasminogen activ ators, Even in the presence of epsilon-aminocaproic acid (EACA) and fi brinogen fragments, allosteric effecters for Glu-plasminogen, slaplabi n increased the activation of both forms of plasminogen. In size-exclu sion chromatography of Glu-plasminogen and Lys-plasminogen, the molecu lar elution time, which varies as the conformation of a protein change s, was shortened by staplabin, These results suggest that staplabin ca uses plasminogens to be more susceptible to activation and fibrin bind ing by inducing a conformational change that is, at least in part, dif ferent From that induced by EACA and fibrinogen fragments. (C) 1997 Fe deration of European Biochemical Societies.