An active zymogen: unravelling the mystery of tissue-type plasminogen activator.
In contrast to almost all other proteinases, human tissue-type plasminogen activator (tPA) is also proteolytically active in its zymogen or single-chain form. The closely related plasminogen activator isolated from vampire bat saliva (vPA) acts exclusively in the single-chain form, lacking the requisite cleavage site for proteolytic activation. Recent structural studies on the proteolytic domains of vPA and human tPA in two- and single-chain forms reveal the mechanism of this anomalous activity. The PA-catalyzed proteolytic conversion of plasminogen to plasmin, responsible for the initiation of fibrinolysis, is fibrin-dependent; comparative structural analysis of the plasminogen activators provides clues as to the role of fibrin as cofactor.
Stubbs
M T
MT
Institut für Pharmazeutische Chemie der Philipps-Universität Marburg, Germany.
Renatus
M
M
Bode
W
W
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002384:Catalysis; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000737:chemistry / Q000378:metabolism*; D005337:Fibrin / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D010959:Tissue Plasminogen Activator / Q000737:chemistry / Q000378:metabolism*
D004792:Enzyme Precursors; D005337:Fibrin; D010959:Tissue Plasminogen Activator