PMID: 8962059Dec 10, 1996Paper

Identification of surface residues mediating tissue factor binding and catalytic function of the serine protease factor VIIa

Proceedings of the National Academy of Sciences of the United States of America
C D DickinsonW Ruf

Abstract

Factor VIIa (VIIa), the serine protease that initiates the coagulation pathways, is catalytically activated upon binding to its cell surface receptor and cofactor tissue factor (TF). This study provides a comprehensive analysis of the functional surface of VIIa by alanine scanning mutagenesis of 112 residues. Residue side chains were defined which contribute to TF binding and factor X hydrolysis. Energetically important binding contacts at the interface with TF were identified in the first epidermal growth factor domain of VIIa (Gln-64, Ile-69, Phe-71, Arg-79) and in the protease domain (Arg-277, Met-306, Asp-309). The observed energetic defects are in good agreement with the corresponding residues in TF, suggesting that the VIIa light chain plays a prominent role in high affinity binding of cofactor. Mutation of protease domain interface residues indicated that TF allosterically influences the active site of VIIa. Stabilization of a labile zymogen to enzyme transition could explain the activating effect of TF on VIIa catalytic function. Residues important for factor X hydrolysis were found in three regions of the protease domain: (i) specificity determinants in the catalytic cleft and adjacent loops, (ii) an exosite near the T...Continue Reading

References

Oct 1, 1979·The Journal of Clinical Investigation·D S FairT S Edgington
Apr 1, 1992·Proteins·A L MorrisJ M Thornton
Jan 1, 1992·Analytical Biochemistry·W P Deng, J A Nickoloff
Oct 29, 1991·Biochemistry·E W DavieW Kisiel
Sep 18, 1990·Biochemistry·J A Wells
Jan 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·M A NaviaK Hoogsteen
Apr 5, 1988·Journal of Molecular Biology·R J Read, M N James
Apr 20, 1967·Biochemical and Biophysical Research Communications·I Schechter, A Berger
Oct 10, 1995·Proceedings of the National Academy of Sciences of the United States of America·H BrandstetterW Bode
Jul 1, 1995·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·D M MartinW Ruf
Jul 14, 1995·The Journal of Biological Chemistry·M TsiangC S Gibbs
Sep 22, 1995·The Journal of Biological Chemistry·E Di CeraA Tulinsky
Aug 5, 1993·Journal of Molecular Biology·K PadmanabhanW Kisiel
Jun 1, 1993·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·S SridharaM A Blajchman
Jul 5, 1996·The Journal of Biological Chemistry·R J Baugh, S Krishnaswamy

❮ Previous
Next ❯

Citations

Jan 4, 2001·Human Mutation·J H McVeyE G Tuddenham
Mar 27, 2002·Journal of Computational Chemistry·Lalith PereraLee G Pedersen
Feb 14, 2002·Trends in Cardiovascular Medicine·Charles Eigenbrot, Daniel Kirchhofer
Nov 1, 1997·Trends in Cardiovascular Medicine·D Kirchhofer, D W Banner
Feb 28, 2004·Trends in Cardiovascular Medicine·E Di Cera
Feb 28, 2004·Trends in Cardiovascular Medicine·W Ruf, C D Dickinson
Jun 29, 2011·Biochemistry·Weiling NiuEnrico Di Cera
Mar 14, 2012·Biochemistry·Chandrashekhara ManithodyAlireza R Rezaie
Nov 5, 1997·Nature Biotechnology·A VindigniE Di Cera
Apr 2, 1999·European Journal of Biochemistry·L C PetersenP O Freskgård
Feb 12, 2004·Seminars in Hematology·Egon Persson
Apr 15, 2010·The Journal of Biological Chemistry·Katrine S LarsenLars C Petersen
Jan 26, 2012·The Journal of Biological Chemistry·Lisbeth M AndersenEgon Persson
Jul 22, 2008·The Journal of Biological Chemistry·Jais R BjelkeEgon Persson
Jun 13, 2000·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·E Persson
Mar 3, 2005·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·Jacqueline A CutlerGeoffrey F Savidge
Jun 13, 2000·Protein Science : a Publication of the Protein Society·L C PetersenE Persson
Feb 10, 2012·Thrombosis and Haemostasis·Ramón MontesJosé Hermida
Oct 7, 2004·Biological & Pharmaceutical Bulletin·Hiroko ShibataYasuo Tsutsumi
Jun 7, 2006·American Journal of Clinical Pathology·Eleanor S PollakKenneth A Bauer
Jun 28, 2011·Laboratory Hematology : Official Publication of the International Society for Laboratory Hematology·A GirolamiS Vettore
Jun 2, 2012·Frontiers in Bioscience (Landmark Edition)·Kanagasabai Vadivel, S Paul Bajaj
Jun 7, 2014·Annual Review of Biochemistry·Laura E Sanman, Matthew Bogyo
Jul 8, 1999·Proceedings of the National Academy of Sciences of the United States of America·Z HuA Garen
Oct 28, 2005·Proceedings of the National Academy of Sciences of the United States of America·Kanika BajajRaghavan Varadarajan
Nov 8, 2001·Proceedings of the National Academy of Sciences of the United States of America·E PerssonO H Olsen
Aug 4, 1999·Proceedings of the National Academy of Sciences of the United States of America·A C PikeE Persson
Mar 28, 2008·Journal of Drug Targeting·Mamoru ShojiJames P Snyder
Jul 6, 2011·Trends in Biotechnology·David W Gohara, Enrico Di Cera
Mar 17, 2009·Blood Cells, Molecules & Diseases·Younan ChenJingqiu Cheng
May 17, 2005·Journal of Thrombosis and Haemostasis : JTH·V WilliamsonB J Clarke
Apr 21, 2005·Protein Science : a Publication of the Protein Society·Henry R MaunRobert A Lazarus
Oct 26, 2005·Journal of Thrombosis and Haemostasis : JTH·M J PageE Di Cera

❮ Previous
Next ❯

Related Concepts

Related Feeds

Birth Defects

Birth defects encompass structural and functional alterations that occur during embryonic or fetal development and are present since birth. The cause may be genetic, environmental or unknown and can result in physical and/or mental impairment. Here is the latest research on birth defects.

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.