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Title page for ETD etd-07152011-200536

Type of Document Master's Thesis
Author Davis, Mary Elizabeth
Author's Email Address mary.beth.davis@vanderbilt.edu
URN etd-07152011-200536
Title Characterization of fibrinogen-binding surface protein B and staphylocoagulase in human blood fibrinolysis and coagulation
Degree Master of Science
Department Pathology
Advisory Committee
Advisor Name Title
Paul E. Bock, Ph.D. Committee Chair
Ingrid Verhamme, Ph.D. Committee Member
Richard Hoover, Ph.D. Committee Member
  • staphylocoagulase
  • acute bacterial endocarditis
  • Streptococcus agalactiae
  • Fibrinogen-binding surface protein B
  • bacterial virulence factors
  • blood coagulation
  • serine protease
  • fibrinolysis
Date of Defense 2011-07-01
Availability unrestricted
Characterization of fibrinogen-binding surface protein B (FbsB) in human blood coagulation and fibrinolysis, and of the NH2-terminal dipeptide of staphylocoagulase (SC) in conformational prothrombin activation are presented in this thesis. FbsB was hypothesized to bind fibrinogen and to be a member of the Zymogen Activator and Adhesion Protein (ZAAP) family. Kinetic assays, affinity and size-exclusion chromatography experiments, and Western blots performed in these studies determined that FbsB neither binds fibrinogen nor belongs to the ZAAP family. However, it was concluded that FbsB binds human plasmin and plasminogen, significantly inhibits the rate of plasmin substrate hydrolysis, and enhances plasminogen activation in the presence of tissue-type plasminogen activator. FbsB may be only the second characterized Streptococcus agalactiae protein capable of contributing to the spread of infection through its interaction with human fibrinolytic proteins.

There remains a gap in knowledge about the importance of the sequence of the NH2-terminal dipeptide of SC in conformational prothrombin activation and the impact these conserved residues have in physiological serine protease activation. Kinetic assays with 29 different NH2-terminal SC(1-246) mutants revealed the relative promiscuity of these residues in prothrombin activation. Seven of the mutants screened activate prothrombin with 100-160% of the activity of wild-type. This data, along with future studies, may provide vital information about the mechanisms of prothrombin activation, and serine protease zymogen activation in general.

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