Localization of a metal-dependent epitope to the amino terminal residues 33-40 of human factor IX

Thrombosis Research
W F CheungK J Smith

Abstract

Metal binding sites within the Gla domain of vitamin K-dependent coagulation factors have been divided into nonspecific metal sites and calcium-specific sites. We demonstrate here that five residues within the Gla domain of factor IX are responsible for the reactivity with the metal-dependent factor IX monoclonal antibody, A-7. First we demonstrate that modifying any one of three residues within this site in factor IX abolishes the binding of A-7. To confirm the specificity of the antibody, the Gla domain of factor VII was changed at residues 32, 33, 34, 38 and 39 to the homologous residues of human factor IX. These changes were sufficient to generate a factor VII Gla domain with an A-7 binding site of the same affinity as that in factor IX. The site identified is one of the two major surfaces of the Gla domain and may represent the metal-dependent binding site.

References

Jan 1, 1977·Annual Review of Biochemistry·J Stenflo, J W Suttie
Jul 1, 1977·The Journal of General Virology·F L GrahamR Nairn
Mar 1, 1987·American Journal of Clinical Pathology·K J SmithL F Smith
Jan 1, 1985·Annual Review of Biochemistry·J W Suttie
Jan 1, 1985·Haematologia·C Vermeer, M A De Boer-Van den Berg
Jun 16, 1995·The Journal of Biological Chemistry·F SekiyaT Morita

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Citations

Jan 1, 1997·Protein Science : a Publication of the Protein Society·S GillisM D Bond
Nov 8, 2017·Proceedings of the National Academy of Sciences of the United States of America·Anders L NielsenHenrik Østergaard

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