title: An active zymogen: unravelling the mystery of tissue-type plasminogen activator.
abstract: 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.
authors.affiliation: Institut für Pharmazeutische Chemie der Philipps-Universität Marburg, Germany.
authors.forename: M T
authors.initials: MT
authors.lastname: Stubbs
authors.forename: M
authors.initials: M
authors.lastname: Renatus
authors.forename: W
authors.initials: W
authors.lastname: Bode
mesh_terms: 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*
chemical_list: D004792:Enzyme Precursors; D005337:Fibrin; D010959:Tissue Plasminogen Activator