1bf9
N-TERMINAL EGF-LIKE DOMAIN FROM HUMAN FACTOR VII, NMR, 23 STRUCTURES
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OverviewOverview
Blood coagulation is initiated by Ca(2+)-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, gamma-carboxyglutamic-acid-containing (Gla) domain followed by two, epidermal growth factor (EGF) like domains, the first of which can bind, one Ca2+ ion (Kd approximately 150 microM) 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 Ca(2+)-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 Ca(2+)-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, Ca(2+)-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.
DiseaseDisease
Known diseases associated with this structure: Factor VII deficiency OMIM:[227500], Myocardial infarction, decreased susceptibility to OMIM:[227500]
About this StructureAbout this Structure
1BF9 is a Single protein structure of sequence from Homo sapiens. Active as Coagulation factor VIIa, with EC number 3.4.21.21 Full crystallographic information is available from OCA.
ReferenceReference
Solution structure of the N-terminal EGF-like domain from human factor VII., Muranyi A, Finn BE, Gippert GP, Forsen S, Stenflo J, Drakenberg T, Biochemistry. 1998 Jul 28;37(30):10605-15. PMID:9692950
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