Factor VII central. A novel mutation in the catalytic domain that reduces tissue factor binding, impairs activation by factor Xa, and abolishes amidolytic and coagulant activity.

The Journal of Biological Chemistry
D BharadwajW Kisiel

Abstract

Factor VII is a vitamin K-dependent zymogen of a serine protease that participates in the initial phase of blood coagulation. A factor VII molecular variant (factor VII Central) was identified in a 24-year-old male with severe factor VII deficiency and whose plasma factor VII antigen was 38% of normal, but expressed <1% factor VII procoagulant activity. DNA sequence analysis of the patient's factor VII gene revealed a thymidine to cytidine transition at nucleotide 10907 in exon VIII that results in a novel amino acid substitution of Phe328 to Ser. The patient was homozygous for this mutation, whereas each parent of the patient was heterozygous for this mutation. To investigate the molecular properties of this variant, a recombinant F328S factor VII mutant was prepared and analyzed in relation to wild-type factor VII. F328S factor VII exhibited <1% factor VII procoagulant activity and a 2-fold decreased affinity for tissue factor and failed to activate factor X or IX in the presence of tissue factor following activation by factor Xa. In addition, F328S factor VIIa exhibited no detectable amidolytic activity in the presence of tissue factor. The rate of F328S factor VII activation by factor Xa was markedly decreased relative to t...Continue Reading

References

Oct 29, 1991·Biochemistry·E W DavieW Kisiel
Nov 28, 1989·Biochemistry·A H PedersenL C Petersen
Aug 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·P J O'HaraM J Murray
Apr 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·F S HagenK Kurachi
Jan 1, 1980·Methods in Enzymology·E Engvall
Jan 1, 1981·American Journal of Hematology·M V RagniU Hasiba
Aug 5, 1993·Journal of Molecular Biology·K PadmanabhanW Kisiel

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Citations

Jan 4, 2001·Human Mutation·J H McVeyE G Tuddenham
Mar 27, 2002·Journal of Computational Chemistry·Lalith PereraLee G Pedersen
Nov 1, 1997·Trends in Cardiovascular Medicine·D Kirchhofer, D W Banner
Feb 28, 2004·Trends in Cardiovascular Medicine·W Ruf, C D Dickinson
Jun 16, 2009·Biochimie·Ieva SutkeviciuteVladas A Bumelis
Nov 2, 1999·Journal of Structural Biology·G Kemball-CookK Harlos
Apr 21, 2001·European Journal of Human Genetics : EJHG·M Giansily-BlaizotUNKNOWN Study Group of Factor Seven Deficiency
Mar 15, 2015·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·Hui LiuYu Hu
Nov 4, 2008·Haemophilia : the Official Journal of the World Federation of Hemophilia·F H HerrmannUNKNOWN Greifswald Factor FVII Deficiency Study Group
May 20, 1998·Archives of Biochemistry and Biophysics·M IinoW Kisiel

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