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Coagulation factor
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PDB id
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1cfi
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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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Biochemistry
34:12126-12137
(1995)
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PubMed id:
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Structure of the calcium ion-bound gamma-carboxyglutamic acid-rich domain of factor IX.
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S.J.Freedman,
B.C.Furie,
B.Furie,
J.D.Baleja.
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ABSTRACT
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We have determined the Ca(II)-bound structure of factor IX, residues 1-47, by
nuclear magnetic resonance (NMR) spectroscopy. The amino-terminal 47 residues
include the gamma-carboxyglutamic acid-rich and aromatic amino acid stack
domains, and this region is responsible for Ca(II)-dependent phospholipid
binding in factor IX. Protons in the 1-47 amino acid sequence were assigned
using standard two-dimensional homonuclear NMR experiments. A total of 851
distance restraints and 57 torsion angle restraints were used to generate 17
final structures by distance geometry and simulated annealing methods. The
backbone RMSD to the geometric average is 0.6 +/- 0.1 A. The Ca(II)-bound
structure is substantially more ordered with increased helical content compared
to the apo-factor IX (1-47) structure. The global fold is similar to the crystal
structure of the Ca(II)-bound Gla domain of prothrombin fragment I from residues
12 to 47 (RMSD approximately 1.3 A), but the backbone conformation differs in
the first 11 residues, particularly between residues 3 and 6. The amino-terminal
nine Gla residues are oriented to the interior of the protein and suggest an
internal Ca(II) binding pocket. The carboxyl-terminal three Gla residues are
exposed to solvent. The majority of hydrophobic residues are required to
stabilize a globular core in the carboxyl-terminal three-quarters of the
molecule. However, a hydrophobic surface patch in the amino-terminal region may
represent a phospholipid binding site in factor IX.
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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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S.Mukherjee,
A.Saha,
P.Biswas,
C.Mandal,
and
K.Ray
(2008).
Structural analysis of factor IX protein variants to predict functional aberration causing haemophilia B.
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Haemophilia, 14,
1076-1081.
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I.Hasanbasic,
I.Rajotte,
and
M.Blostein
(2005).
The role of gamma-carboxylation in the anti-apoptotic function of gas6.
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J Thromb Haemost, 3,
2790-2797.
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K.Hansson,
and
J.Stenflo
(2005).
Post-translational modifications in proteins involved in blood coagulation.
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J Thromb Haemost, 3,
2633-2648.
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R.J.Preston,
A.Villegas-Mendez,
Y.H.Sun,
J.Hermida,
P.Simioni,
H.Philippou,
B.Dahlbäck,
and
D.A.Lane
(2005).
Selective modulation of protein C affinity for EPCR and phospholipids by Gla domain mutation.
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FEBS J, 272,
97.
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H.Deguchi,
S.Yegneswaran,
and
J.H.Griffin
(2004).
Sphingolipids as bioactive regulators of thrombin generation.
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| |
J Biol Chem, 279,
12036-12042.
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M.A.Grant,
K.Hansson,
B.C.Furie,
B.Furie,
J.Stenflo,
and
A.C.Rigby
(2004).
The metal-free and calcium-bound structures of a gamma-carboxyglutamic acid-containing contryphan from Conus marmoreus, glacontryphan-M.
|
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J Biol Chem, 279,
32464-32473.
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M.Huang,
B.C.Furie,
and
B.Furie
(2004).
Crystal structure of the calcium-stabilized human factor IX Gla domain bound to a conformation-specific anti-factor IX antibody.
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J Biol Chem, 279,
14338-14346.
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PDB code:
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M.D.Blostein,
B.C.Furie,
I.Rajotte,
and
B.Furie
(2003).
The Gla domain of factor IXa binds to factor VIIIa in the tenase complex.
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J Biol Chem, 278,
31297-31302.
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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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S.X.Wang,
E.Hur,
C.A.Sousa,
L.Brinen,
E.J.Slivka,
and
R.J.Fletterick
(2003).
The extended interactions and Gla domain of blood coagulation factor Xa.
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Biochemistry, 42,
7959-7966.
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PDB code:
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Y.Shikamoto,
T.Morita,
Z.Fujimoto,
and
H.Mizuno
(2003).
Crystal structure of Mg2+- and Ca2+-bound Gla domain of factor IX complexed with binding protein.
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J Biol Chem, 278,
24090-24094.
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PDB codes:
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H.Mizuno,
Z.Fujimoto,
H.Atoda,
and
T.Morita
(2001).
Crystal structure of an anticoagulant protein in complex with the Gla domain of factor X.
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Proc Natl Acad Sci U S A, 98,
7230-7234.
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PDB code:
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T.M.Hackeng,
J.A.Fernández,
P.E.Dawson,
S.B.Kent,
and
J.H.Griffin
(2000).
Chemical synthesis and spontaneous folding of a multidomain protein: anticoagulant microprotein S.
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Proc Natl Acad Sci U S A, 97,
14074-14078.
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M.Y.Wong,
J.A.Gurr,
and
P.N.Walsh
(1999).
The second epidermal growth factor-like domain of human factor IXa mediates factor IXa binding to platelets and assembly of the factor X activating complex.
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Biochemistry, 38,
8948-8960.
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H.Atoda,
M.Ishikawa,
H.Mizuno,
and
T.Morita
(1998).
Coagulation factor X-binding protein from Deinagkistrodon acutus venom is a Gla domain-binding protein.
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Biochemistry, 37,
17361-17370.
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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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P.O.Freskgârd,
L.C.Petersen,
D.A.Gabriel,
X.Li,
and
E.Persson
(1998).
Conformational stability of factor VIIa: biophysical studies of thermal and guanidine hydrochloride-induced denaturation.
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Biochemistry, 37,
7203-7212.
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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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R.S.Roy,
S.Kim,
J.D.Baleja,
and
C.T.Walsh
(1998).
Role of the microcin B17 propeptide in substrate recognition: solution structure and mutational analysis of McbA1-26.
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Chem Biol, 5,
217-228.
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PDB code:
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S.S.Ahmad,
M.Y.Wong,
R.Rawala,
B.A.Jameson,
and
P.N.Walsh
(1998).
Coagulation factor IX residues G4-Q11 mediate its interaction with a shared factor IX/IXa binding site on activated platelets but not the assembly of the functional factor X activating complex.
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Biochemistry, 37,
1671-1679.
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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.Mathur,
D.Zhong,
A.K.Sabharwal,
K.J.Smith,
and
S.P.Bajaj
(1997).
Interaction of factor IXa with factor VIIIa. Effects of protease domain Ca2+ binding site, proteolysis in the autolysis loop, phospholipid, and factor X.
|
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J Biol Chem, 272,
23418-23426.
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J.F.McDonald,
A.M.Shah,
R.A.Schwalbe,
W.Kisiel,
B.Dahlbäck,
and
G.L.Nelsestuen
(1997).
Comparison of naturally occurring vitamin K-dependent proteins: correlation of amino acid sequences and membrane binding properties suggests a membrane contact site.
|
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Biochemistry, 36,
5120-5127.
|
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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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S.Gillis,
B.C.Furie,
B.Furie,
H.Patel,
M.C.Huberty,
M.Switzer,
W.B.Foster,
H.A.Scoble,
and
M.D.Bond
(1997).
gamma-Carboxyglutamic acids 36 and 40 do not contribute to human factor IX function.
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Protein Sci, 6,
185-196.
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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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P.O.Freskgård,
O.H.Olsen,
and
E.Persson
(1996).
Structural changes in factor VIIa induced by Ca2+ and tissue factor studied using circular dichroism spectroscopy.
|
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Protein Sci, 5,
1531-1540.
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S.J.Freedman,
D.G.Sanford,
W.W.Bachovchin,
B.C.Furie,
J.D.Baleja,
and
B.Furie
(1996).
Structure and function of the epidermal growth factor domain of P-selectin.
|
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Biochemistry, 35,
13733-13744.
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PDB code:
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S.J.Freedman,
M.D.Blostein,
J.D.Baleja,
M.Jacobs,
B.C.Furie,
and
B.Furie
(1996).
Identification of the phospholipid binding site in the vitamin K-dependent blood coagulation protein factor IX.
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J Biol Chem, 271,
16227-16236.
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PDB code:
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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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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
code is
shown on the right.
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Links
