Structural biology of factor VIIa/tissue factor initiated coagulation.
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.
Protein Science Laboratory, UCLA/Orthopaedic Hospital, Department of Orthopaedic Surgery, University of California, Los Angeles, CA 90095-1795, USA.
Kanagasabai
K
Vadivel
S Paul
SP
Bajaj
D001665:Binding Sites; D001777:Blood Coagulation / Q000502:physiology*; D001779:Blood Coagulation Factors / Q000737:chemistry / Q000378:metabolism; D002412:Cations / Q000378:metabolism; D015942:Factor VIIa / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008074:Lipoproteins / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000737:chemistry; D017510:Protein Folding; D054730:Protein Interaction Domains and Motifs; D013925:Thromboplastin / Q000737:chemistry* / Q000378:metabolism*
D001779:Blood Coagulation Factors; D002412:Cations; D008074:Lipoproteins; D046912:Multiprotein Complexes; C051928:lipoprotein-associated coagulation inhibitor; D013925:Thromboplastin; D015942:Factor VIIa