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Laboratory of Barbara Furie and Bruce Furie, Harvard Medical School
Directors: Barbara C. Furie, Bruce Furie
Visiting and Adjunct Scientists: Dr. Alan Rigby, Harvard; Dr. Johan Stenflo, Lund; Dr. Leisa Stenberg, Harvard; Dr.Mark Brown, Harvard
Contact: Tel: 508 289-7270 | Email: bfurie@mbl.edu
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g-Carboxyglutamic acid is a calcium-binding amino acid well-distributed among mammalian species, but the search for this amino acid in invertebrates has not been revealing, with a single exception: toxins from the predatory marine cone snails, Conus. The biosynthesis of g-carboxyglutamic acid in the mammalian vitamin K-dependent proteins has been studied extensively in our laboratory at Harvard Medical School, with recent emphasis on the cloning, structure, and enzymology of the g-carboxylase and the mechanistic role of vitamin K. The synthesis of this amino acid is critical for normal blood coagulation in that all of the vitamin K-dependent blood coagulation proteins contain g-carboxyglutamic acid, an amino acid that is required for biological activity.
With the discovery of g-carboxyglutamic acid in conotoxins isolated from the venoms of predatory marine snails belonging to the genus Conus, the question arises as to the pathway of biosynthesis of this amino acid and comparison of invertebrate and mammalian g-carboxylation systems. At our MBL laboratory, we study invertebrate g-carboxyglutamic acid biosynthesis in a unique marine animal that synthesizes g-carboxyglutamic acid. This carboxylase has an absolute requirement for vitamin K. The goals are to isolate and clone this enzyme, to determine the amino acid sequence homology to the mammalian carboxylase, and to understand its mechanism of action in fixing carbon dioxide to glutamic acid.
Furthermore, the laboratory has identified and cloned a series of novel g-carboxyglutamic acid-containing conopeptides and determined their amino acid sequence and three dimensional structure by 2D NMR spectroscopy.
Adjunct Scientist Bruce Furie
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Education:
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| 1970 |
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M.D. University of Pennsylvania School of Medicine |
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| 1966 |
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A.B. Chemistry, Princeton University |
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Adjunct Scientist Barbara Furie
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Education:
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| 1970 |
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Ph.D. Chemistry,University of Pennsylvania |
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| 1964 |
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B.S. Chemistry,New York University |
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Recent Publications:
Sathish, J, Falati, S., Croce, K., Crump, C., Furie, B.C., Furie, B. and Poole, A.W. Crosslinking of platelet-bound rPSGL-Ig induces calcium signaling through clustering of Pselectin and Fc(RIIA. Submitted.
Falati, S., Gross, P.L., Merrill-Skoloff, G., Sim, D., Faumenhaft, R., Celi, A., Furie, B.C. and Furie, B. In vivo models of platelet function and thrombosis: study of real-time thrombus formation. Meth. Molec. Medicine (Gibbins, J.M. and Mahaut-Smith, M.P., ed.). Humana, in press (2003).
Hirata, T., Furie, B.C. and Furie, B.: P-, E- and L-selectin mediate migration of activated CD8+ T lymphocytes into inflamed skin. J. Immunol. 169:4307-4313, 2002.
Falati, S., Gross, P., Merrill-Skoloff, G., Furie, B.C. and Furie, B.: Real time in vivo imaging of platelets, tissue factor and fibrin during arterial thrombus formation in the mouse. Nature Medicine 8:1175-1181, 2002.
Brown, M., Hambe, B., Furie, B., Furie, B.C., Stenflo, J. and Stenberg, L. M. Detection of vitamin K-dependent proteins in venoms with a monoclonal antibody specific for g-carboxyglutamic acid. Toxicon 40:447-453, 2002. |
