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Crystal structure of factor Vai and method for identifying blood factor Va modulators

United States Patent Application

20060014934
A1
View the Complete Application at the US Patent & Trademark Office
The present invention shows the crystal structure of protein C inactivated factor Va (A1-A3-C1-C2) that depicts a novel domain arrangement. The newly disclosed orientation has implications for binding to membranes essential for function. A high-affinity calcium binding site and a copper binding site have been identified, neither of which show a direct involvement in chain association. This structure represents the largest physiologically relevant fragment of factor Va solved to date and provides a new scaffold for generation of models of coagulation factors.
Everse, Stephen J. (Shelburne, VT), Adams, Ty E. (Cambridge, GB), Hockin, Matthew F. (Salt Lake City, UT), Mann, Kenneth G. (Grand Isle, VT)
11/ 131,091
May 17, 2005
[0001] This work was supported by grants from the National Institutes of Health, HL64891 and HL34575 Department of Energy Grant ER45828. The Government has certain rights in the invention. This application claims benefit of U.S. Provisional Application Ser. No. 60/572,040 filed May 18, 2004. [0002] The atomic coordinates and structure factors have been deposited in the protein databank, www.rcsb.org (PDB ID code 1SDD).