Abstract

This is a revision of a proposal to continue support to study various aspects of the biochemistry of the transglutaminases, factor XIII and tissue transglutaminase.
The aim i s to determine structural features that govern the stability of these proteins and to understand the various intermolecular associations that regulate their functions. The proposal contains four Specific Aims: 1)control mechanisms operating i fibrin stabilization, 2)enzyme mechanistic studies on FXIIIA , 3) identification of donor sites in the 2 chains of human fibrin(ogen) reacting with Factor XIIIa, and 4) further identification of binding domains involved in the interaction of transglutaminase to human plasma fibronectin.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL002212-43
Application #
6030350
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
1974-10-01
Project End
2001-06-30
Budget Start
1999-07-01
Budget End
2001-06-30
Support Year
43
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
Northwestern University at Chicago
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611

  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
Murthy, S N; Wilson, J H; Lukas, T J et al. (1998) Cross-linking sites of the human tau protein, probed by reactions with human transglutaminase. J Neurochem 71:2607-14

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