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.
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