PDBsum entry: 1mgx

Coagulation factor

PDB id: 1mgx

Contents

Protein chain

47 a.a.

PDB id:

1mgx

Name:

Coagulation factor

Title:

Coagulation factor, mg(ii), nmr, 7 structures (backbone atoms only)

Structure:

Coagulation factor ix. Chain: a. Fragment: the gla and aromatic amino acid stack domains from residues 1 - 47. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606

NMR struc:

7 models

Authors:

S.J.Freedman,B.C.Furie,B.Furie,J.D.Baleja

Key ref:

S.J.Freedman et al. (1996). Identification of the phospholipid binding site in the vitamin K-dependent blood coagulation protein factor IX. J Biol Chem, 271, 16227-16236. PubMed id: 8663165 DOI: 10.1074/jbc.271.27.16227

Date:

21-Jun-95 Release date: 08-Nov-96

Protein chain

P00740  (FA9_HUMAN) -  Coagulation factor IX

Seq: 461 a.a.

Struc: 47 a.a.*

* PDB and UniProt seqs differ at 12 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.3.4.21.22 - Coagulation factor IXa.
• Reaction: Hydrolyzes one Arg-|-Ile bond in factor X to form factor Xa.

 Gene Ontology (GO) functional annotation 

• Cellular component: extracellular region (1 term)
• Biochemical function: calcium ion binding (1 term)

DOI no: 10.1074/jbc.271.27.16227

J Biol Chem 271:16227-16236 (1996)

PubMed id: 8663165

Identification of the phospholipid binding site in the vitamin K-dependent blood coagulation protein factor IX.

S.J.Freedman, M.D.Blostein, J.D.Baleja, M.Jacobs, B.C.Furie, B.Furie.

ABSTRACT

The blood coagulation and regulatory proteins that contain gamma-carboxyglutamic acid are a part of a unique class of membrane binding proteins that require calcium for their interaction with cell membranes. Following protein biosynthesis, glutamic acids on these proteins are converted to gamma-carboxyglutamic acid (Gla) in a reaction that requires vitamin K as a cofactor. The vitamin K-dependent proteins undergo a conformational transition upon metal ion binding, but only calcium ions mediate protein-phospholipid interaction. To identify the site on Factor IX that is required for phospholipid binding, we have determined the three-dimensional structure of the Factor IX Gla domain bound to magnesium ions by NMR spectroscopy. By comparison of this structure to that of the Gla domain bound to calcium ions, we localize the membrane binding site to a highly ordered structure including residues 1-11 of the Gla domain. In the presence of Ca2+, Factor IX Gla domain peptides that contain the photoactivatable amino acid p-benzoyl-L-phenylalanine at positions 6 or 9 cross-link to phospholipid following irradiation, while peptides lacking this amino acid analog or with this analog at position 46 did not cross-link. These results indicate that the NH2 terminus of the Gla domain, specifically including leucine 6 and phenylalanine 9 in the hydrophobic patch, is the contact surface on Factor IX that interacts with the phospholipid bilayer.

Selected figure(s)

Figure 7.
Fig. 7. A, chemical structure of Bpa. B, chemical synthesis of Factor IX (1-47) peptides containing benzoyl-L-phenylalanine. Bpa, a photoreactive homolog of phenylalanine, was incorporated into peptides using solid phase synthesis and Fmoc chemistry. Bpa was substituted for leucine 6 (Factor IX (1-47)/Bpa 6), for phenylalanine 9 (Factor IX (1-47)/Bpa 9), and for valine 46 (Factor IX (1-47)/Bpa 46). Bpa, - .

Figure 11.
Fig. 11. Hypothetical model of the interaction of Factor IX and phospholipid membranes. In this model, the hydrophobic residues (black) that form the hydrophobic patch in the phospholipid binding site of Factor IX are buried in the phospholipid bilayer. Specific residues in the Gla domain interact with the phospholipid head groups and are responsible for the requirement for anionic phospholipids for effective binding.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (1996, 271, 16227-16236) copyright 1996.

Figures were selected by an automated process.