Thrombin pp 3-61 | Cite as

X-Ray Crystal Structures of Human α-Thrombin and of the Human Thrombin-Hirudin Complex

  • Wolfram Bode
  • Robert Huber
  • Timothy J. Rydel
  • Alexander Tulinsky


α-Thrombin is a glycosylated trypsinlike serine proteinase (Magnusson, 1971), generated in the penultimate step of the blood coagulation cascade from the circulating plasma protein prothrombin. Upon autocatalytic and factor Xa cleavage, the functional two-chain molecule α-thrombin is generated. In the case of the human species this consists of the 36-residue A chain and the 259-residue B chain (Butkowski et al., 1977; Thompson et al., 1977; Walz et al., 1977; Degen et al., 1983). The two chains are covalently connected by a disulfide bridge. The B chain carries an asparagine-linked sugar chain (Fenton et al., 1977a; Butkowski et al., 1977); it has also been shown to be homologous to the catalytic domains of other pancreatic and coagulation/fibrinolytic trypsinlike proteinases (Jackson and Nemerson, 1980). Upon further autolytic or proteolytic cleavage, more species (in particular β- and γ-thrombin) are generated which retain some activity against small synthetic substrates, but have lost most or all clotting activity (Lundblad et al., 1979; Fenton, 1981, 1986; Berliner, 1984; Elion et al., 1986; Hofsteenge et al., 1988).


Bovine Thrombin Recombinant Hirudin Bovine Trypsin Human Thrombin Loop Segment 
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Copyright information

© Springer Science+Business Media New York 1992

Authors and Affiliations

  • Wolfram Bode
    • 1
  • Robert Huber
    • 1
  • Timothy J. Rydel
    • 2
  • Alexander Tulinsky
    • 2
  1. 1.Max-Planck-Institut für BiochemieMartinsriedGermany
  2. 2.Department of ChemistryMichigan State UniversityEast LansingUSA

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