Journal
FRONTIERS IN BIOSCIENCE-LANDMARK
Volume 17, Issue -, Pages 2476-2494Publisher
FRONTIERS IN BIOSCIENCE INC
DOI: 10.2741/4066
Keywords
Blood Coagulation; Tissue Factor; Factor VIIa; Factors IX and X; Structural Biology; Review
Categories
Funding
- NHLBI NIH HHS [R56 HL036365, R21 HL089661] Funding Source: Medline
Ask authors/readers for more resources
Factor VII (FVII) consists of an N-terminal gamma-carboxyglutamic acid domain followed by two epidermal growth factor-like (EGF1 and EGF2) domains and the C-terminal protease domain. Activation of FVII results in a two-chain FVIIa molecule consisting of a light chain (Gla-EGF1-EGF2 domains) and a heavy chain (protease domain) held together by a single disulfide bond. During coagulation, the complex of tissue factor (TF, a transmembrane glycoprotein) and FVIIa activates factor IX (FIX) and factor X (FX). FVIIa is structurally zymogen-like and when bound to TF, it is more active enzyme-like. FIX and FX share structural homology with FVII. Three structural biology aspects of FVIIa/TF are presented in this review. One, regions in soluble TF (sTF) that interact with FVIIa as well as mapping of Ca2+, Mg2+, Na+ and Zn2+ sites in FVIIa and their functions; two, modeled interactive regions of Gla and EGF1 domains of FXa and FIXa with FVIIa/sTF; and three, incompletely formed oxyanion hole in FVIIa/sTF and its induction by substrate/inhibitor. Finally, an overview of the recognition elements in TF pathway inhibitor is provided.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available