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• W2006128594 endingPage "10615" @default.
• W2006128594 startingPage "10605" @default.
• W2006128594 abstract "Blood coagulation is initiated by Ca2+-dependent binding of coagulation factor VIIa (FVIIa) to its cofactor, tissue factor (TF). The TF:FVIIa complex activates factors IX and X, ultimately leading to the formation of thrombin and the coagulation of blood. FVII consists of an N-terminal γ-carboxyglutamic-acid-containing (Gla) domain followed by two epidermal growth factor (EGF) like domains, the first of which can bind one Ca2+ ion (Kd ≈ 150 μM) and a C-terminal serine protease domain. Using 1H nuclear magnetic resonance spectroscopy, we have determined the solution structure of a synthetic N-terminal EGF-like domain (EGF1) of human FVII (residues 45−85) in the absence of Ca2+. A comparison of this structure of apo EGF1 with the Ca2+-bound EGF1 in the complex of FVIIa and TF [Banner, D. W., et al. (1996) Nature 380, 41−46] suggests that the structural changes in the EGF1 domain upon Ca2+ binding are minor and are concentrated near the Ca2+-binding site, which is facing away from the TF interaction surface. Amino acid side chains that are crucial for the binding of FVII to TF show a similar conformation in both structures and are therefore unlikely to directly influence the Ca2+-dependent binding of FVII to TF. As Ca2+ binding to EGF1 does not lead to a conformational change in the residues constituting the interaction surface for binding to TF, our results are consistent with the idea that the altered orientation between the Gla and EGF1 domains that result from Ca2+ binding is responsible for the increased affinity of FVII/FVIIa for TF." @default.
• W2006128594 created "2016-06-24" @default.
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• W2006128594 date "1998-07-01" @default.
• W2006128594 modified "2023-10-03" @default.
• W2006128594 title "Solution Structure of the N-Terminal EGF-like Domain from Human Factor VII^," @default.
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• W2006128594 doi "https://doi.org/10.1021/bi980522f" @default.
• W2006128594 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/9692950" @default.
• W2006128594 hasPublicationYear "1998" @default.
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