Although the application is listed as an R-01, the work described in the application is a continuation of a previous R-01 that became a subproject in a Program Project Grant at the Mayo Clinic and subsequently moved to the University of Vermont as Project 1 in the Vermont Specialized Center for Research in Thrombosis. Dr. Mann's specific aims are to: quantitate protein-protein interactions involved in prothrombinase and other vitamin K dependent complexes; to evaluate the tissue factor (TF)/VIIa complex in terms of physical and kinetic interactions; to evaluate factor Xa/thrombomodulin interactions; to study surface dependent coagulation reactions using total internal reflectance fluorescence (TIRF); and to image coagulation enzymes adn complexes using high resolution electron microscopy and crystallography. The applicant described in detail the reagents and methods to be used; the experimental design and anticipated results. Much of the application is based on the hypothesis that the coagulation reactions on membranes are examples of a channeled enzymatic process in which the products of one enzymatic process rearranges on the membrane surface to form a succeeding enzyme complex rather than being transported through solution.
| Lecompte, M F; Bouix, G; Mann, K G (1994) Electrostatic and hydrophobic interactions are involved in factor Va binding to membranes containing acidic phospholipids. J Biol Chem 269:1905-10 |
| Mann, K G (1994) The coagulation explosion. Ann N Y Acad Sci 714:265-9 |
| Swords, N A; Mann, K G (1993) The assembly of the prothrombinase complex on adherent platelets. Arterioscler Thromb 13:1602-12 |
| Butenas, S; Orfeo, T; Lawson, J H et al. (1992) Aminonaphthalenesulfonamides, a new class of modifiable fluorescent detecting groups and their use in substrates for serine protease enzymes. Biochemistry 31:5399-411 |
| Procyk, R; Medved, L; Engelke, K J et al. (1992) Nonclottable fibrin obtained from partially reduced fibrinogen: characterization and tissue plasminogen activator stimulation. Biochemistry 31:2273-8 |
| Mann, K G; Lawson, J H (1992) The role of the membrane in the expression of the vitamin K-dependent enzymes. Arch Pathol Lab Med 116:1330-6 |
