Modifications of Extrinsic Pathway Inhibitor (EPI) and Factor Xa that Affect their Ability to Interact and to Inhibit Factor Vila/Tissue Factor: Evidence for a Two-Step Model of Inhibition-Reference-Cited by-同舟云学术

Modifications of Extrinsic Pathway Inhibitor (EPI) and Factor Xa that Affect their Ability to Interact and to Inhibit Factor Vila/Tissue Factor: Evidence for a Two-Step Model of Inhibition

Published:1988 Issue:03 Volume:60 Page:453-456
ISSN:0340-6245
Container-title:Thrombosis and Haemostasis
language:en
Short-container-title:Thromb Haemost

Author:

Warn-Cramer Bonnie J¹,Vijaya Mohan Rao L¹,Maki Steven L¹,Rapaport Samuel I¹

Affiliation:

1. The Departments of Medicine and Pathology, University of California at San Diego, La Jolla, CA, USA

Abstract

SummaryInhibition of factor VIIa/tissue factor (TF) by extrinsic pathway inhibitor (EPI) requires the participation of factor Xa. Through this inhibition, factor Xa generated initially may feed back to suppress continuing generation of factor Xa via the extrinsic pathway during hemostasis. We have utilized chemical modifications of EPI and factor Xa to study the reactions responsible for inhibition. The data are consistent with a two-step model. First, EPI binds to factor Xa in a Ca2+ independent reaction in which the gla-domain of factor Xa does not participate. A functional active site on factor Xa and arginine residues on EPI are essential for this step. Then the factor Xa/EPI complex binds to factor VIIa/TF with resultant inhibition of its enzymatic activity. The gla-domain of factor Xa is essential for this step. Intact positively charged lysines on factor Xa may also be important

Publisher

Georg Thieme Verlag KG

Subject

Hematology

Link

http://www.thieme-connect.de/products/ejournals/pdf/10.1055/s-0038-1646989.pdf

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