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-fold the plasminogen activator-catalyzed activation of Glu-plasminogen and Lys-plasminogen as well as their binding to fibrin. Staplabin was not stimulatory to the amidolytic activity of plasmin and plasminogen activators. Even in the presence of epsilon-aminocaproic acid (EACA) and fibrinogen fragments, allosteric effectors for Glu-plasminogen, staplabin increased the activation of both forms of plasminogen. In size-exclusion chromatography of Glu-plasminogen and Lys-plasminogen, the molecular elution time, which varies as the conformation of a protein changes, was shortened by staplabin. These results suggest that staplabin causes plasminogens to be more susceptible to activation and fibrin binding by inducing a conformational change that is, at least in part, different from that induced by EACA and fibrinogen fragments.
Takayasu
R
R
Department of Applied Biological Science, Tokyo Noko University, Fuchu, Japan.
Hasumi
K
K
Shinohara
C
C
Endo
A
A
D000494:Allosteric Regulation; D015119:Aminocaproic Acid / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology*; D004789:Enzyme Activation; D005337:Fibrin / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism; D005341:Fibrinolysin / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D010958:Plasminogen / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D010960:Plasminogen Activators / Q000494:pharmacology*; D011487:Protein Conformation / Q000187:drug effects*; D011760:Pyrrolidinones / Q000494:pharmacology*; D013917:Thrombin / Q000378:metabolism
D001578:Benzopyrans; D010446:Peptide Fragments; D011760:Pyrrolidinones; C018998:lysyl-plasminogen; C103026:staplabin; D005337:Fibrin; D005340:Fibrinogen; D010958:Plasminogen; D010960:Plasminogen Activators; D013917:Thrombin; D005341:Fibrinolysin; D015119:Aminocaproic Acid