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PDBsum entry 1ccf
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Coagulation factor
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PDB id
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1ccf
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* Residue conservation analysis
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Enzyme class:
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E.C.3.4.21.6
- coagulation factor Xa.
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Reaction:
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Preferential cleavage: Arg-|-Thr and then Arg-|-Ile bonds in prothrombin to form thrombin.
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J Biol Chem
267:19642-19649
(1992)
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PubMed id:
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How an epidermal growth factor (EGF)-like domain binds calcium. High resolution NMR structure of the calcium form of the NH2-terminal EGF-like domain in coagulation factor X.
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M.Selander-Sunnerhagen,
M.Ullner,
E.Persson,
O.Teleman,
J.Stenflo,
T.Drakenberg.
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ABSTRACT
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Domains homologous to the epidermal growth factor (EGF) are important building
blocks for extracellular proteins. Proteins containing these domains have been
shown to function in such diverse biological processes as blood coagulation,
complement activation, and the developmental determination of embryonic cell
fates. Many of these proteins require calcium for their biological function. In
the case of coagulation factors IX and X and anticoagulants proteins C and S,
calcium has been found to bind to the EGF-like domains. We have now determined
the three-dimensional structure of the calcium-bound form of the NH2-terminal
EGF-like domain in coagulation factor X by two-dimensional NMR and simulated
folding. Ligands to the calcium ion are the two backbone carbonyls in Gly-47 and
Gly-64, as well as the side chains in Gln-49, erythro-beta-hydroxyaspartic acid
(Hya) 63, and possibly Asp-46. The conserved Asp-48 is not a ligand in our
present structures. The remaining ligands are assumed to be solvent molecules
or, in the intact protein, ligands from neighboring domains. Other proteins
interacting in a calcium-dependent manner may also contribute ligands. A
comparison with the calcium-free form shows that calcium binding induces
strictly local structural changes in the domain. Residues corresponding to the
side chain ligands in factor X are conserved in many other proteins, such as the
integral membrane protein TAN-1 of human lymphocytes and its developmentally
important homolog, Notch, in Drosophila. Calcium binding to EGF-like domains may
be crucial for numerous protein-protein interactions involving EGF-like domains
in coagulation factors, plasma proteins, and membrane proteins. Therefore, there
is reason to believe that this novel calcium site plays an important role in the
biochemistry of extracellular proteins.
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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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E.Di Schiavi,
E.Riano,
B.Heye,
P.Bazzicalupo,
and
E.I.Rugarli
(2005).
UMODL1/Olfactorin is an extracellular membrane-bound molecule with a restricted spatial expression in olfactory and vomeronasal neurons.
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Eur J Neurosci,
21,
3291-3300.
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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.Sørensen,
S.Thiel,
and
J.C.Jensenius
(2005).
Mannan-binding-lectin-associated serine proteases, characteristics and disease associations.
|
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Springer Semin Immunopathol,
27,
299-319.
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T.M.Misenheimer,
and
D.F.Mosher
(2005).
Biophysical characterization of the signature domains of thrombospondin-4 and thrombospondin-2.
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J Biol Chem,
280,
41229-41235.
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R.A.Salzman,
H.Koiwa,
J.I.Ibeas,
J.M.Pardo,
P.M.Hasegawa,
and
R.A.Bressan
(2004).
Inorganic cations mediate plant PR5 protein antifungal activity through fungal Mnn1- and Mnn4-regulated cell surface glycans.
|
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Mol Plant Microbe Interact,
17,
780-788.
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B.R.Lentz
(2003).
Exposure of platelet membrane phosphatidylserine regulates blood coagulation.
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Prog Lipid Res,
42,
423-438.
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B.Zhou,
J.A.Weigel,
A.Saxena,
and
P.H.Weigel
(2002).
Molecular cloning and functional expression of the rat 175-kDa hyaluronan receptor for endocytosis.
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Mol Biol Cell,
13,
2853-2868.
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D.Venkateswarlu,
L.Perera,
T.Darden,
and
L.G.Pedersen
(2002).
Structure and dynamics of zymogen human blood coagulation factor X.
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Biophys J,
82,
1190-1206.
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P.N.Robinson,
P.Booms,
S.Katzke,
M.Ladewig,
L.Neumann,
M.Palz,
R.Pregla,
F.Tiecke,
and
T.Rosenberg
(2002).
Mutations of FBN1 and genotype-phenotype correlations in Marfan syndrome and related fibrillinopathies.
|
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Hum Mutat,
20,
153-161.
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A.Muranyi,
J.Evenäs,
Y.Stenberg,
J.Stenflo,
and
T.Drakenberg
(2000).
Characterization of the EGF-like module pair 3-4 from vitamin K-dependent protein S using NMR spectroscopy reveals dynamics on three separate time scales and extensive effects from calcium binding.
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Biochemistry,
39,
15742-15756.
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M.Osterlund,
R.Owenius,
E.Persson,
M.Lindgren,
U.Carlsson,
P.O.Freskgård,
and
M.Svensson
(2000).
Spectroscopic probing of the influence of calcium and the gla domain on the interaction between the first EGF domain in factor VIIa and tissue factor.
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Eur J Biochem,
267,
6204-6211.
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P.N.Robinson,
and
M.Godfrey
(2000).
The molecular genetics of Marfan syndrome and related microfibrillopathies.
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J Med Genet,
37,
9.
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C.Valcarce,
I.Björk,
and
J.Stenflo
(1999).
The epidermal growth factor precursor. A calcium-binding, beta-hydroxyasparagine containing modular protein present on the surface of platelets.
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Eur J Biochem,
260,
200-207.
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F.Vella,
J.F.Hernandez,
A.Molla,
M.R.Block,
and
G.J.Arlaud
(1999).
Grafting an RGD motif onto an epidermal growth factor-like module: chemical synthesis and functional characterization of the chimeric molecule.
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J Pept Res,
54,
415-426.
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J.Jin,
J.Chang,
J.Y.Chang,
R.F.Kelley,
D.W.Stafford,
and
D.L.Straight
(1999).
Factor VIIa's first epidermal growth factor-like domain's role in catalytic activity.
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Biochemistry,
38,
1185-1192.
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L.Perera,
T.A.Darden,
and
L.G.Pedersen
(1999).
Probing the structural changes in the light chain of human coagulation factor VIIa due to tissue factor association.
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Biophys J,
77,
99.
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Y.H.Kao,
G.F.Lee,
Y.Wang,
M.A.Starovasnik,
R.F.Kelley,
M.W.Spellman,
and
L.Lerner
(1999).
The effect of O-fucosylation on the first EGF-like domain from human blood coagulation factor VII.
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Biochemistry,
38,
7097-7110.
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PDB codes:
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A.Muranyi,
B.E.Finn,
G.P.Gippert,
S.Forsén,
J.Stenflo,
and
T.Drakenberg
(1998).
Solution structure of the N-terminal EGF-like domain from human factor VII.
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Biochemistry,
37,
10605-10615.
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PDB code:
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B.Bersch,
J.F.Hernandez,
D.Marion,
and
G.J.Arlaud
(1998).
Solution structure of the epidermal growth factor (EGF)-like module of human complement protease C1r, an atypical member of the EGF family.
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Biochemistry,
37,
1204-1214.
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PDB code:
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D.Tolkatchev,
and
F.Ni
(1998).
Calcium binding properties of an epidermal growth factor-like domain from human thrombomodulin.
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Biochemistry,
37,
9091-9100.
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K.Kamata,
H.Kawamoto,
T.Honma,
T.Iwama,
and
S.H.Kim
(1998).
Structural basis for chemical inhibition of human blood coagulation factor Xa.
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Proc Natl Acad Sci U S A,
95,
6630-6635.
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PDB codes:
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R.A.Montgomery,
M.T.Geraghty,
E.Bull,
B.D.Gelb,
M.Johnson,
I.McIntosh,
C.A.Francomano,
and
H.C.Dietz
(1998).
Multiple molecular mechanisms underlying subdiagnostic variants of Marfan syndrome.
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Am J Hum Genet,
63,
1703-1711.
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M.D.Rand,
A.Lindblom,
J.Carlson,
B.O.Villoutreix,
and
J.Stenflo
(1997).
Calcium binding to tandem repeats of EGF-like modules. Expression and characterization of the EGF-like modules of human Notch-1 implicated in receptor-ligand interactions.
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Protein Sci,
6,
2059-2071.
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Y.Stenberg,
K.Julenius,
I.Dahlqvist,
T.Drakenberg,
and
J.Stenflo
(1997).
Calcium-binding properties of the third and fourth epidermal-growth-factor-like modules in vitamin-K-dependent protein S.
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Eur J Biochem,
248,
163-170.
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A.K.Downing,
V.Knott,
J.M.Werner,
C.M.Cardy,
I.D.Campbell,
and
P.A.Handford
(1996).
Solution structure of a pair of calcium-binding epidermal growth factor-like domains: implications for the Marfan syndrome and other genetic disorders.
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Cell,
85,
597-605.
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PDB codes:
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C.E.White,
M.J.Hunter,
D.P.Meininger,
S.Garrod,
and
E.A.Komives
(1996).
The fifth epidermal growth factor-like domain of thrombomodulin does not have an epidermal growth factor-like disulfide bonding pattern.
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Proc Natl Acad Sci U S A,
93,
10177-10182.
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G.Hjälm,
E.Murray,
G.Crumley,
W.Harazim,
S.Lundgren,
I.Onyango,
B.Ek,
M.Larsson,
C.Juhlin,
P.Hellman,
H.Davis,
G.Akerström,
L.Rask,
and
B.Morse
(1996).
Cloning and sequencing of human gp330, a Ca(2+)-binding receptor with potential intracellular signaling properties.
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Eur J Biochem,
239,
132-137.
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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.Maurer,
E.Hohenester,
and
J.Engel
(1996).
Extracellular calcium-binding proteins.
|
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Curr Opin Cell Biol,
8,
609-617.
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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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R.Hrabal,
Z.Chen,
S.James,
H.P.Bennett,
and
F.Ni
(1996).
The hairpin stack fold, a novel protein architecture for a new family of protein growth factors.
|
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Nat Struct Biol,
3,
747-752.
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R.Tejero,
D.Bassolino-Klimas,
R.E.Bruccoleri,
and
G.T.Montelione
(1996).
Simulated annealing with restrained molecular dynamics using CONGEN: energy refinement of the NMR solution structures of epidermal and type-alpha transforming growth factors.
|
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Protein Sci,
5,
578-592.
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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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T.Sasaki,
K.Mann,
G.Murphy,
M.L.Chu,
and
R.Timpl
(1996).
Different susceptibilities of fibulin-1 and fibulin-2 to cleavage by matrix metalloproteinases and other tissue proteases.
|
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Eur J Biochem,
240,
427-434.
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C.M.Kielty,
and
C.A.Shuttleworth
(1995).
Fibrillin-containing microfibrils: structure and function in health and disease.
|
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Int J Biochem Cell Biol,
27,
747-760.
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D.P.Meininger,
M.J.Hunter,
and
E.A.Komives
(1995).
Synthesis, activity, and preliminary structure of the fourth EGF-like domain of thrombomodulin.
|
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Protein Sci,
4,
1683-1695.
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PDB code:
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G.Nijbroek,
S.Sood,
I.McIntosh,
C.A.Francomano,
E.Bull,
L.Pereira,
F.Ramirez,
R.E.Pyeritz,
and
H.C.Dietz
(1995).
Fifteen novel FBN1 mutations causing Marfan syndrome detected by heteroduplex analysis of genomic amplicons.
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Am J Hum Genet,
57,
8.
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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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M.Sunnerhagen,
S.Forsén,
A.M.Hoffrén,
T.Drakenberg,
O.Teleman,
and
J.Stenflo
(1995).
Structure of the Ca(2+)-free Gla domain sheds light on membrane binding of blood coagulation proteins.
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Nat Struct Biol,
2,
504-509.
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Y.S.Wu,
V.L.Bevilacqua,
and
J.M.Berg
(1995).
Fibrillin domain folding and calcium binding: significance to Marfan syndrome.
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Chem Biol,
2,
91-97.
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Z.Rao,
P.Handford,
M.Mayhew,
V.Knott,
G.G.Brownlee,
and
D.Stuart
(1995).
The structure of a Ca(2+)-binding epidermal growth factor-like domain: its role in protein-protein interactions.
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Cell,
82,
131-141.
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PDB code:
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D.M.Milewicz
(1994).
Identification of defects in the fibrillin gene and protein in individuals with the Marfan syndrome and related disorders.
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Tex Heart Inst J,
21,
22-29.
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E.Pöschl,
J.W.Fox,
D.Block,
U.Mayer,
and
R.Timpl
(1994).
Two non-contiguous regions contribute to nidogen binding to a single EGF-like motif of the laminin gamma 1 chain.
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EMBO J,
13,
3741-3747.
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L.Karttunen,
M.Raghunath,
L.Lönnqvist,
and
L.Peltonen
(1994).
A compound-heterozygous Marfan patient: two defective fibrillin alleles result in a lethal phenotype.
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Am J Hum Genet,
55,
1083-1091.
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M.T.Stubbs,
and
W.Bode
(1994).
Coagulation factors and their inhibitors.
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Curr Opin Struct Biol,
4,
823-832.
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S.Jia,
K.McGinnis,
W.J.VanDusen,
C.J.Burke,
A.Kuo,
P.R.Griffin,
M.K.Sardana,
K.O.Elliston,
A.M.Stern,
and
P.A.Friedman
(1994).
A fully active catalytic domain of bovine aspartyl (asparaginyl) beta-hydroxylase expressed in Escherichia coli: characterization and evidence for the identification of an active-site region in vertebrate alpha-ketoglutarate-dependent dioxygenases.
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Proc Natl Acad Sci U S A,
91,
7227-7231.
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T.C.Pan,
T.Sasaki,
R.Z.Zhang,
R.Fässler,
R.Timpl,
and
M.L.Chu
(1993).
Structure and expression of fibulin-2, a novel extracellular matrix protein with multiple EGF-like repeats and consensus motifs for calcium binding.
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J Cell Biol,
123,
1269-1277.
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E.Persson,
and
J.Stenflo
(1992).
Comparison of the Ca2+ binding properties of the gamma-carboxyglutamic acid-containing module of protein Z in the intact protein and in N-terminal fragments.
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FEBS Lett,
314,
5-9.
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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
