An active zymogen: unravelling the mystery of tissue-type plasminogen activator

Biol Chem. 1998 Feb;379(2):95-103. doi: 10.1515/bchm.1998.379.2.95.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Catalysis
  • Enzyme Activation
  • Enzyme Precursors / chemistry
  • Enzyme Precursors / metabolism*
  • Fibrin / metabolism
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Conformation
  • Tissue Plasminogen Activator / chemistry
  • Tissue Plasminogen Activator / metabolism*


  • Enzyme Precursors
  • Fibrin
  • Tissue Plasminogen Activator