PDBsum entry 1bf9

Blood coagulation

PDB id: 1bf9

Contents

Protein chain

41 a.a.

References listed in PDB file

Key reference

Title

Solution structure of the n-Terminal egf-Like domain from human factor VII.

Authors

A.Muranyi, B.E.Finn, G.P.Gippert, S.Forsén, J.Stenflo, T.Drakenberg.

Ref.

Biochemistry, 1998, 37, 10605-10615. [DOI no: 10.1021/bi980522f]

PubMed id

9692950

Abstract

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.

Secondary reference #1

Title

The crystal structure of the complex of blood coagulation factor viia with soluble tissue factor.

Authors

D.W.Banner, A.D'Arcy, C.Chène, F.K.Winkler, A.Guha, W.H.Konigsberg, Y.Nemerson, D.Kirchhofer.

Ref.

Nature, 1996, 380, 41-46.

PubMed id

8598903

Secondary reference #2

Title

The three-Dimensional structure of the first egf-Like module of human factor IX: comparison with egf and tgf-Alpha.

Authors

M.Baron, D.G.Norman, T.S.Harvey, P.A.Handford, M.Mayhew, A.G.Tse, G.G.Brownlee, I.D.Campbell.

Ref.

Protein Sci, 1992, 1, 81-90. [DOI no: 10.1002/pro.5560010109]

PubMed id

1304885

Figure 2.
Fig. 2. Experimentalrestraints. A: Experimentaldata used to identifysecondarystructure. Black boxesrepresentHN,HN<,,i-,, andHN,Ha(,,,-,,NOEs.Theheightoftheboxrelatestothe size oftheNOE(strong,medium,weak).Openboxesrepresent NOEs romprolineH6protons. S ndicatesresidueswhosebackboeaideprotonswere slow to xchange in D20, ad * in- icates 3JHN ouplingconstantsgreaterthan 9 Hz. B: Thedistribution f long-range andshort-rangedistancerestraints. barsrepresentlong-rangedistancerestraints(>i - [i + 1); openbarsrepresentshort-rangedistancerestraints(

Figure 3.
Fig. 3. Distribution of NOE restraint energy forstructures produced by restrained simulated annealing (i.e., prior o final minimization). Re- straint energies are in kJ/mol; selection cutoff at 369 kJ/mol, denoted by a

The above figures are reproduced from the cited reference which is an Open Access publication published by the Protein Society

Secondary reference #3

Title

Three-Dimensional structure of the apo form of the n-Terminal egf-Like module of blood coagulation factor X as determined by nmr spectroscopy and simulated folding.

Authors

M.Ullner, M.Selander, E.Persson, J.Stenflo, T.Drakenberg, O.Teleman.

Ref.

Biochemistry, 1992, 31, 5974-5983. [DOI no: 10.1021/bi00141a004]

PubMed id

1627540