Paul Bock

Regulation of blood coagulation proteolytic enzymes

Research in this laboratory is focused on elucidating the molecular mechanisms of human blood coagulation and fibrinolysis. Biochemical and biophysical techniques are being used to determine how the proteolytic enzymes of blood coagulation and fibrinolysis are regulated through interactions with specific proteins and other regulatory macromolecules, and the membrane surfaces of vascular cells. Present work focuses on four areas: (1) the mechanism by which factor Va regulates the formation of the active blood clotting proteinase, thrombin, from its inactive precursor, prothrombin, (2) the mechanisms that regulate the specificity of thrombin for its physiological substrates and inhibitors, (3) the mechanism of conformational activation of prothrombin by staphylocoagulase and its role in the molecular pathology of endocarditis, and (4) the mechanism of activation of plasminogen by streptokinase, which is the basis for the use of streptokinase as a thrombolytic drug. Fluorescence spectroscopy, protein chemistry, enzyme kinetics, and molecular biology techniques are being used to define the roles of protein conformational changes and the assembly of macromolecular complexes in these mechanisms. The goal of the research is to develop molecular descriptions of the regulation of these systems, which is necessary for understanding the mechanism of the normal hemostatic response and the molecular pathology of thrombosis.

Lab Homepage