PMID: 9539719May 16, 1998Paper

Manipulation of the membrane binding site of vitamin K-dependent proteins: enhanced biological function of human factor VII

Proceedings of the National Academy of Sciences of the United States of America
A M ShahG L Nelsestuen

Abstract

Recent studies suggested that modification of the membrane contact site of vitamin K-dependent proteins may enhance the membrane affinity and function of members of this protein family. The properties of a factor VII mutant, factor VII-Q10E32, relative to wild-type factor VII (VII, containing P10K32), have been compared. Membrane affinity of VII-Q10E32 was about 20-fold higher than that of wild-type factor VII. The rate of autoactivation VII-Q10E32 with soluble tissue factor was 100-fold faster than wild-type VII and its rate of activation by factor Xa was 30 times greater than that of wild-type factor VII. When combined with soluble tissue factor and phospholipid, activated factor VII-Q10E32 displayed increased activation of factor X. Its coagulant activity was enhanced in all types of plasma and with all sources of tissue factor tested. This difference in activity (maximum 50-fold) was greatest when coagulation conditions were minimal, such as limiting levels of tissue factor and/or phospholipid. Because of its enhanced activity, factor VII-Q10E32 and its derivatives may provide important reagents for research and may be more effective in treatment of bleeding and/or clotting disorders.

References

Dec 1, 1977·Proceedings of the National Academy of Sciences of the United States of America·B Osterud, S I Rapaport
May 30, 1978·Biochemistry·G L NelsestuenR G Di Scipio
Nov 4, 1975·Biochemistry·W Kisiel, E W Davie
Mar 19, 1992·The New England Journal of Medicine·B Furie, B C Furie
Nov 28, 1989·Biochemistry·A H PedersenL C Petersen
Sep 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·L V Rao, S I Rapaport
Oct 1, 1971·Biochemical and Biophysical Research Communications·G L Nelsestuen, J W Suttie
Jan 1, 1995·Advances in Experimental Medicine and Biology·S GlazerJ F Falch
Jan 1, 1996·Haemostasis·U Hedner
Feb 4, 2005·Journal of Health Politics, Policy and Law·Mark Schlesinger

❮ Previous
Next ❯

Citations

Nov 30, 2006·European Biophysics Journal : EBJ·Olivier Taboureau, Ole Hvilsted Olsen
Feb 14, 2002·Trends in Cardiovascular Medicine·Charles Eigenbrot, Daniel Kirchhofer
Jul 25, 2012·Biophysical Journal·Y Zenmei OhkuboEmad Tajkhorshid
Mar 8, 2005·Blood Reviews·Evangelos TerposAmin Rahemtulla
Jul 25, 2013·Biochemistry·Narjes TavoosiJames H Morrissey

❮ Previous
Next ❯

Related Concepts

Related Feeds

Blood Clotting Disorders

Thrombophilia includes conditions with increased tendency for excessive blood clotting. Blood clotting occurs when the body has insufficient amounts of specialized proteins that make blood clot and stop bleeding. Here is the latest research on blood clotting disorders.