Bonno N Bouma

Publications (23)99.23 Total impact

• Article: Thrombin-Activatable Fibrinolysis Inhibitor (TAFI, Plasma Procarboxypeptidase B, Procarboxypeptidase R, Procarboxypeptidase U)

  Bonno N. Bouma, Pauline F. Marx, Laurent O. Mosnier, Joost C.M. Meijers
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  ABSTRACT: Recently, a new inhibitor of fibrinolysis was described. This inhibitor downregulated fibrinolysis after it was activated by thrombin, and was therefore named TAFI (thrombin-activatable fibrinolysis inhibitor; EC 3.4.17.20). TAFI turned out to be identical to previously described proteins, procarboxypeptidase U, procarboxypeptidase R, and plasma procarboxypeptidase B. In this overview, the protein will be referred to as TAFI. TAFI is a procarboxypeptidase and a member of the family of metallocarboxypeptidases. These enzymes are circulating in plasma and are present in several tissues such as pancreas. In this review, we will describe the properties of basic carboxypeptidases with the emphasis on the role of TAFI in coagulation and fibrinolysis. It cannot be ruled out, however, that TAFI has other, yet undefined, functions in biology.
  Thrombosis Research.
• Article: Thrombin activatable fibrinolysis inhibitor (TAFI) at the interface between coagulation and fibrinolysis.

  Bonno N Bouma, Laurent O Mosnier
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  ABSTRACT: The thrombin-catalysed conversion of plasma fibrinogen into fibrin and the development of an insoluble fibrin clot are the final steps of the coagulation cascade during haemostasis. A delicate balance between coagulation and fibrinolysis determines the stability of the fibrin clot. Thrombin Activatable Fibrinolysis Inhibitor (TAFI) plays an important role in this process. TAFI is activated by thrombin and protects the fibrin clot against lysis. The role of TAFI in bleeding and thrombotic disorders is discussed as well as its novel emerging role in wound healing and inflammation.
  Pathophysiology of Haemostasis and Thrombosis 33(5-6):375-81. · 2.23 Impact Factor
• Article: Involvement of Amino Acid Residues 423–429 of Human Protein S in Binding to C4b-Binding Protein

  José A. Fernández, John H. Griffin, Glenn T.G. Chang, Jeanette Stam, Pieter H. Reitsma, Rogier M. Bertina, Bonno N. Bouma
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  ABSTRACT: ABSTRACT: Human protein S binds to C4b-binding protein (C4BP) both in plasma and in a system using purified proteins. Amino acid residues 420-434 of the first disulfide loop of the sex hormone binding globulinlike domain of protein S are involved in the interaction of protein S with C4BP. To define the involvement of specific polar amino acids within residues 420-434, we studied in parallel synthetic protein S peptides and recombinant protein S variants containing the same amino acid replacements, K423E, E424K, Q427E and K429E. Synthetic peptide analogs of peptide PSP-420 (residues 420-434) were assayed for binding C4BP and as inhibitors of complex formation. The PSP-420 peptide and the analogous peptide with the substitution E424K, but not the peptides containing the substitutions K423E and K429E, were able to bind C4BP. Recombinant proteins with mutations of K423E, Q427E and K429E showed reduced affinity for C4BP compared to plasma protein S, recombinant wild type protein S, or E424K-protein S. These results suggest that Lys-423, Gln-427 and Lys-429 of protein S are important for normal binding to C4BP. The anti-protein S monoclonal antibody LJ-56, raised against peptide PSP-420, recognizes only free protein S and inhibits complex formation with C4BP. Antibody LJ-56 recognized the E424K and Q427E peptides but not the K423E or K429E peptides. Similarly, the E424K and Q427E protein S mutants were recognized by LJ-56, whereas the K423E and K429E protein S mutants were not recognized. This suggests that both in the peptide PSP-420 and in protein S, Lys-423 and Lys-429 significantly contribute to binding to antibody LJ-56. These results demonstrate that protein S residues 423, 427 and 429, but not residue 424, are involved in binding to both the antibody LJ-56 and to C4BP. When peptides PSP 420 and SL-6 (residues 447-460) with carboxyterminal amide or carboxylate moieties were compared to their ability to inhibit C4BP-protein S complexation, PSP-420-amide was the most potent. This finding together with the other results described here supports the hypothesis that the residues 420 and 434 in protein S provides a major binding site for C4BP
  Blood Cells, Molecules, and Diseases.