Abstract

This proposal deals with fundamental problems of human blood coagulation using a combined protein, enzyme and organic chemical approach. Specifically, its thrust is directed toward the following subjects. I. Elucidation of the molecular details of the pathways of activation of Factor XIII, including the newly recognized thrombin-independent pathway. Particular emphasis will be given to the regulatory role of fibrinogen on the thrombin-dependent pathway. II. Kinetic and mechanistic studies on Factor XIIIa. III. Novel procedures for the labelling and isolation of cross-linking sites of native protein substrates of Factor XIIIa and of related transamidating enzymes. IV. The rheological as well as thrombolytic evaluation of specific inhibitors of fibrin cross-linking. V. Comparative studies regarding the role and control of transamidating enzymes in clotting.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL002212-31
Application #
3334119
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
1974-10-01
Project End
1989-11-30
Budget Start
1985-12-01
Budget End
1986-11-30
Support Year
31
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
Northwestern University at Chicago
Department
Type
Schools of Arts and Sciences
DUNS #
City
Evanston
State
IL
Country
United States
Zip Code
60208

  Publications

Hang, Jun; Zemskov, Evgeny A; Lorand, Laszlo et al. (2005) Identification of a novel recognition sequence for fibronectin within the NH2-terminal beta-sandwich domain of tissue transglutaminase. J Biol Chem 280:23675-83
Murthy, S N Prasanna; Iismaa, Siiri; Begg, Gillian et al. (2002) Conserved tryptophan in the core domain of transglutaminase is essential for catalytic activity. Proc Natl Acad Sci U S A 99:2738-42
Lorand, L (2001) Factor XIII: structure, activation, and interactions with fibrinogen and fibrin. Ann N Y Acad Sci 936:291-311
Murthy, S N; Lorand, L (2000) Nucleotide binding by the erythrocyte transglutaminase/Gh protein, probed with fluorescent analogs of GTP and GDP. Proc Natl Acad Sci U S A 97:7744-7
Saber-Lichtenberg, Y; Brix, K; Schmitz, A et al. (2000) Covalent cross-linking of secreted bovine thyroglobulin by transglutaminase. FASEB J 14:1005-14
Lorand, L (2000) Sol Sherry Lecture in Thrombosis : research on clot stabilization provides clues for improving thrombolytic therapies. Arterioscler Thromb Vasc Biol 20:9-Feb
Murthy, S N; Wilson, J H; Lukas, T J et al. (2000) Transglutaminase-catalyzed crosslinking of the Aalpha and gamma constituent chains in fibrinogen. Proc Natl Acad Sci U S A 97:44-8
Murthy, S N; Lomasney, J W; Mak, E C et al. (1999) Interactions of G(h)/transglutaminase with phospholipase Cdelta1 and with GTP. Proc Natl Acad Sci U S A 96:11815-9
Lorand, L; Velasco, P T; Murthy, S N et al. (1999) Autoimmune antibody in a hemorrhagic patient interacts with thrombin-activated factor XIII in a unique manner. Blood 93:909-17
Lorand, L; Parameswaran, K N; Murthy, S N (1998) A double-headed Gly-Pro-Arg-Pro ligand mimics the functions of the E domain of fibrin for promoting the end-to-end crosslinking of gamma chains by factor XIIIa. Proc Natl Acad Sci U S A 95:537-41

Showing the most recent 10 out of 36 publications