William V. Sweeney, Ph.D.
Professor - Biochemistry
Office 1321aN, tel 212-772-5335, fax (dept) 212-772-5332, email email@example.com
B.S. Knox College, Ph.D. University of Iowa, Postdoc. University of California at Berkeley
Biophysical Studies of the Epidermal Growth Factor-like Modules in Blood Coagulation Proteins Human vitamin K-dependent blood coagulation factors contain three regions, including a T-carboxyglumatic acid domain, two tandemly connected epidermal growth factor-like (EGF-like) modules, and serine protease domain. Our work focuses on synthetic peptides homologous to the EGF-like modules of human blood coagulation factor IX. Factor IX, also known as Christmas factor, is the precursor of a serine protease required for blood clotting. Clinically, defects in this factor result in hemophilia B, a disorder found in approximately one in 30, 000 males. Human factor IX contains 415 amino acids. However, the two EGF-like modules each contain only slightly more than 40 amino acids. Our laboratory has established that calcium binding required for activity occurs at a site in the first of the two EGF-like modules. Using 2D-NMR techniques, identification of the amino acids involved in this calcium binding is in progress. In addition, the full sequence-specific assignments for the proton NMR spectrum of the first EGF-like domain, human factor IX (45-87), have been reported, and a solution structure determined. Future efforts will be directed toward identification and characterization of the specific functional roles the EGF-like domains play in blood coagulation
Yang, Y., Tam, J.P., Schneider, K., Chait, B.T., Sweeney, W.V. 1994 Two-step selective formation of three disulfide bridges in the C-terminal epidermal growth factor of human blood coagulation factor IX. Protein Sci.3, 1267-1275.
Huang, L.H., Cheng, H., Pardi, A., Tam, J.P., Sweeney, W.V. 1991 1H-NMR assignments, secondary structure, and location of the calcium binding site in the first EGF-like domain of blood coagulation factor IX., Biochemistry30: 7402-7409.
Yang, Y., Sweeney, W.V., Schneider, K.,Thörnquist, S., Chait, B.T., Tam, J.P. (1994) Aspartimide Formation in Base-driven 9-Fluorenylmethoxycarbonyl Chemistry, Tet. Lett. 35, 9684-9692.
Yang, Y., Sweeney, W.V., Thörnquist, S., Schneider, K., Chait, B.T., Tam, J.P. (1994) Characterization of a Side Reaction Using Stepwise Detection in Peptide Detection in Peptide Synthesis with Fmoc Chemistry, Techniques in Protein Chemistry VI (J.Crabb, Eds.), 555-564, Academic Press