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Coagulation factor
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PDB id
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1cfh
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* Residue conservation analysis
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Enzyme class:
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E.C.3.4.21.22
- Coagulation factor IXa.
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Reaction:
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Hydrolyzes one Arg-|-Ile bond in factor X to form factor Xa.
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Gene Ontology (GO) functional annotation
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Cellular component
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extracellular region
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1 term
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Biochemical function
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calcium ion binding
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1 term
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DOI no:
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J Biol Chem
270:7980-7987
(1995)
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PubMed id:
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Structure of the metal-free gamma-carboxyglutamic acid-rich membrane binding region of factor IX by two-dimensional NMR spectroscopy.
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S.J.Freedman,
B.C.Furie,
B.Furie,
J.D.Baleja.
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ABSTRACT
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The gamma-carboxyglutamic acid-rich domain of blood coagulation Factor IX is
required for the binding of the protein to phospholipid membranes. To
investigate the three-dimensional structure of this domain, a synthetic peptide
corresponding to residues 1-47 of Factor IX was studied by 1H NMR spectroscopy.
In the absence of metal ions, the proton chemical shift dispersion in the
one-dimensional NMR spectrum indicated that the peptide contains regular
structural elements. Upon the addition of Ca(II) or Mg(II), large chemical shift
changes were observed in the amide proton and methyl proton regions of the
spectrum, consistent with the conformational transitions that metal ions are
known to induce in native Factor IX. The apopeptide was studied by
two-dimensional NMR spectroscopy at 500 MHz to determine its solution structure.
Protons were assigned using total correlation spectroscopy, nuclear Overhauser
effect spectroscopy, and double quantum-filtered correlation spectroscopy
experiments. Intensities of cross-peaks in the nuclear Overhauser effect
spectrum were used to generate a set of interproton distance restraints. The
structure of the apopeptide was then calculated using distance geometry methods.
There are three structural elements in the apopeptide that are linked by a
flexible polypeptide backbone. These elements include a short amino-terminal
tetrapeptide loop (amino acids 6-9), the disulfide-containing hexapeptide loop
(amino acids 18-23), and a carboxyl-terminal alpha helix (amino acids 37-46).
Amide hydrogen exchange kinetics indicate that the majority of the peptide is
solvent accessible, except in the carboxyl-terminal element. The structured
regions in the apopeptide are insufficient to support phospholipid binding,
indicating the importance of additional structural features in the
Ca(II)-stabilized conformer.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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N.Enjolras,
J.L.Plantier,
M.H.Rodriguez,
M.Rea,
O.Attali,
C.Vinciguerra,
and
C.Negrier
(2004).
Two novel mutations in EGF-like domains of human factor IX dramatically impair intracellular processing and secretion.
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J Thromb Haemost, 2,
1143-1154.
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M.Huang,
A.C.Rigby,
X.Morelli,
M.A.Grant,
G.Huang,
B.Furie,
B.Seaton,
and
B.C.Furie
(2003).
Structural basis of membrane binding by Gla domains of vitamin K-dependent proteins.
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Nat Struct Biol, 10,
751-756.
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PDB codes:
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L.Perera,
T.A.Darden,
and
L.G.Pedersen
(1998).
Trans-cis isomerization of proline 22 in bovine prothrombin fragment 1: a surprising result of structural characterization.
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Biochemistry, 37,
10920-10927.
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R.F.Zwaal,
P.Comfurius,
and
E.M.Bevers
(1998).
Lipid-protein interactions in blood coagulation.
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Biochim Biophys Acta, 1376,
433-453.
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A.C.Rigby,
J.D.Baleja,
B.C.Furie,
and
B.Furie
(1997).
Three-dimensional structure of a gamma-carboxyglutamic acid-containing conotoxin, conantokin G, from the marine snail Conus geographus: the metal-free conformer.
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Biochemistry, 36,
6906-6914.
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PDB code:
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A.L.Lomize,
and
H.I.Mosberg
(1997).
Thermodynamic model of secondary structure for alpha-helical peptides and proteins.
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Biopolymers, 42,
239-269.
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L.Li,
T.A.Darden,
S.J.Freedman,
B.C.Furie,
B.Furie,
J.D.Baleja,
H.Smith,
R.G.Hiskey,
and
L.G.Pedersen
(1997).
Refinement of the NMR solution structure of the gamma-carboxyglutamic acid domain of coagulation factor IX using molecular dynamics simulation with initial Ca2+ positions determined by a genetic algorithm.
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Biochemistry, 36,
2132-2138.
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M.Sunnerhagen,
G.A.Olah,
J.Stenflo,
S.Forsén,
T.Drakenberg,
and
J.Trewhella
(1996).
The relative orientation of Gla and EGF domains in coagulation factor X is altered by Ca2+ binding to the first EGF domain. A combined NMR-small angle X-ray scattering study.
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Biochemistry, 35,
11547-11559.
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PDB codes:
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T.C.Evans,
and
G.L.Nelsestuen
(1996).
Importance of cis-proline 22 in the membrane-binding conformation of bovine prothrombin.
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Biochemistry, 35,
8210-8215.
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H.Brandstetter,
M.Bauer,
R.Huber,
P.Lollar,
and
W.Bode
(1995).
X-ray structure of clotting factor IXa: active site and module structure related to Xase activity and hemophilia B.
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Proc Natl Acad Sci U S A, 92,
9796-9800.
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PDB code:
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
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Links
