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September 1, 1999Journal of Biological ChemistryOpen Access

Thrombin Interacts with Thrombomodulin, Protein C, and Thrombin-activatable Fibrinolysis Inhibitor via Specific and Distinct Domains

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Population

56 purified thrombin mutants

Design

Preclinical

Authors

SHScott W. HallStanford UniversityMNMariko NagashimaYamaguchi UniversityLZLei ZhaoStanford University

Discussion

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Implication

May permit engineering of thrombin variants with dissociated activities; leaves open translation to human therapeutics.

Structured PICO

P
Population
56 purified thrombin mutants (in which 76 charged or polar surface residues on thrombin were mutated to alanine)
I
Intervention
Site-directed mutagenesis of thrombin surface residues
O
Outcome
Identification of key residues mediating the interactions of thrombin with thrombomodulin (TM), protein C, and thrombin-activatable fibrinolysis inhibitor (TAFI)surrogate

Distinct domains in thrombin mediate its interactions with thrombomodulin, protein C, and TAFI, allowing for the dissociation of its selective enzymatic properties via mutagenesis.

Cite This Study

Hall et al. (1999) studied this question.

synapsesocial.com/papers/6a7df86b7bc3bc414599b7e1https://doi.org/10.1074/jbc.274.36.25510
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Also Consider

Synapse has enriched 4 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1TAFI, or Plasma Procarboxypeptidase B, Couples the Coagulation and Fibrinolytic Cascades through the Thrombin-Thrombomodulin Complex1996 · 649 citations
  2. 2Thrombin, Thrombomodulin and TAFI in the Molecular Link Between Coagulation and Fibrinolysis1997 · 262 citations
  3. 3Prothrombin Tokushima, a replacement of arginine-418 by tryptophan that impairs the fibrinogen clotting activity of derived thrombin Tokushima1987 · 47 citations
  4. 4Thrombin Glu-39 restricts the P'3 specificity to nonacidic residues1991 · 91 citations