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* Residue conservation analysis
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J Mol Biol
231:103-118
(1993)
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PubMed id:
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Three-dimensional structure of an anti-steroid Fab' and progesterone-Fab' complex.
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J.H.Arevalo,
E.A.Stura,
M.J.Taussig,
I.A.Wilson.
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ABSTRACT
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The monoclonal anti-progesterone antibody DB3 binds progesterone with nanomolar
affinity (Ka approximately 10(9) M-1), suggesting high specificity. However, DB3
also cross-reacts with similar affinity with a subgroup of structurally
distinct, progesterone-like steroids. Crystals of the unliganded Fab' and
various steroid-Fab' complexes are isomorphous and belong to the hexagonal space
group, P6(4)22, with unit cell dimensions of a = b = 135 A, c = 124 A.
Structures of free and progesterone-bound Fab' have been determined by X-ray
crystallography at 2.7 A resolution using molecular replacement techniques.
Progesterone is bound in a hydrophobic pocket formed mainly by the interaction
of three complementarity determining regions L1, H2 and H3. The orientation of
the ligand in the binding site was aided by both crystallographic and
biochemical analyses of substituted steroids. The indole side-chain of TrpH100
of the DB3 has two different conformations, inter-converting "open" and "closed"
forms of the antibody combining site. The TrpH100 indole thus appears to be
acting as an antibody-derived surrogate ligand for its own hydrophobic binding
pocket. These structures provide the first atomic view of how a steroid
interacts with a protein and offer a structural explanation for the restriction
of the anti-progesterone response to the VGAM3.8 family of VH genes.
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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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V.Janiak,
M.Petersen,
M.Zentgraf,
G.Klebe,
and
A.Heine
(2010).
Structure and substrate docking of a hydroxy(phenyl)pyruvate reductase from the higher plant Coleus blumei Benth.
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Acta Crystallogr D Biol Crystallogr,
66,
593-603.
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PDB code:
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J.Nilmeier,
and
M.Jacobson
(2008).
Multiscale Monte Carlo Sampling of Protein Sidechains: Application to Binding Pocket Flexibility.
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J Chem Theory Comput,
4,
835-846.
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P.Verdino,
C.Aldag,
D.Hilvert,
and
I.A.Wilson
(2008).
Closely related antibody receptors exploit fundamentally different strategies for steroid recognition.
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Proc Natl Acad Sci U S A,
105,
11725-11730.
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PDB codes:
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E.W.Debler,
G.F.Kaufmann,
R.N.Kirchdoerfer,
J.M.Mee,
K.D.Janda,
and
I.A.Wilson
(2007).
Crystal structures of a quorum-quenching antibody.
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J Mol Biol,
368,
1392-1402.
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PDB codes:
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M.He,
M.Hamon,
H.Liu,
A.L.Corper,
and
M.J.Taussig
(2006).
Effects of mutation at the D-JH junction on affinity, specificity, and idiotypy of anti-progesterone antibody DB3.
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Protein Sci,
15,
2141-2148.
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E.W.Debler,
S.Ito,
F.P.Seebeck,
A.Heine,
D.Hilvert,
and
I.A.Wilson
(2005).
Structural origins of efficient proton abstraction from carbon by a catalytic antibody.
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Proc Natl Acad Sci U S A,
102,
4984-4989.
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PDB codes:
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O.Dubreuil,
M.Bossus,
M.Graille,
M.Bilous,
A.Savatier,
M.Jolivet,
A.Ménez,
E.Stura,
and
F.Ducancel
(2005).
Fine tuning of the specificity of an anti-progesterone antibody by first and second sphere residue engineering.
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J Biol Chem,
280,
24880-24887.
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A.Piatesi,
and
D.Hilvert
(2004).
Immunological optimization of a generic hydrophobic pocket for high affinity hapten binding and Diels-Alder activity.
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Chembiochem,
5,
460-466.
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V.Hornak,
and
C.Simmerling
(2003).
Generation of accurate protein loop conformations through low-barrier molecular dynamics.
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Proteins,
51,
577-590.
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J.Valjakka,
K.Takkinenz,
T.Teerinen,
H.Söderlund,
and
J.Rouvinen
(2002).
Structural insights into steroid hormone binding: the crystal structure of a recombinant anti-testosterone Fab fragment in free and testosterone-bound forms.
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J Biol Chem,
277,
4183-4190.
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PDB codes:
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S.Coulon,
J.L.Pellequer,
T.Blachère,
M.Chartier,
E.Mappus,
S.W.Chen Sw,
C.Y.Cuilleron,
and
D.Baty
(2002).
Functional characterization of an anti-estradiol antibody by site-directed mutagenesis and molecular modelling: modulation of binding properties and prominent role of the V(L) domain in estradiol recognition.
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J Mol Recognit,
15,
6.
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V.Kairys,
and
M.K.Gilson
(2002).
Enhanced docking with the mining minima optimizer: acceleration and side-chain flexibility.
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J Comput Chem,
23,
1656-1670.
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D.J.Tantillo,
and
K.N.Houk
(2001).
Canonical binding arrays as molecular recognition elements in the immune system: tetrahedral anions and the ester hydrolysis transition state.
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Chem Biol,
8,
535-545.
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F.Bettsworth,
C.Monnet,
B.Watelet,
N.Battail-Poirot,
B.Gilquin,
M.Jolivet,
A.Menez,
M.Arnaud,
and
F.Ducancel
(2001).
Functional characterization of two anti-estradiol antibodies as deduced from modelling and site-directed mutagenesis experiments.
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J Mol Recognit,
14,
99.
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J.Valjakka,
A.Hemminki,
T.Teerinen,
K.Takkinen,
and
J.Rouvinen
(2000).
X-ray studies of recombinant anti-testosterone Fab fragments: the use of PEG 3350 in crystallization.
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Acta Crystallogr D Biol Crystallogr,
56,
218-221.
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R.D.Kirsch,
D.Beale,
M.He,
A.L.Corper,
U.Krawinkel-Brenig,
and
M.J.Taussig
(2000).
Anti-anti-idiotypic (Ab3) antibodies that bind progesterone-11alpha-bovine serum albumin differ in their combining sites from antibodies raised directly against the antigen.
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Immunology,
100,
152-164.
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S.Spinelli,
L.G.Frenken,
P.Hermans,
T.Verrips,
K.Brown,
M.Tegoni,
and
C.Cambillau
(2000).
Camelid heavy-chain variable domains provide efficient combining sites to haptens.
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Biochemistry,
39,
1217-1222.
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PDB code:
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C.Oefner,
A.Binggeli,
V.Breu,
D.Bur,
J.P.Clozel,
A.D'Arcy,
A.Dorn,
W.Fischli,
F.Grüninger,
R.Güller,
G.Hirth,
H.Märki,
S.Mathews,
M.M ller,
R.G.Ridley,
H.Stadler,
E.Vieira,
M.Wilhelm,
F.Winkler,
and
W.Wostl
(1999).
Renin inhibition by substituted piperidines: a novel paradigm for the inhibition of monomeric aspartic proteinases?
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Chem Biol,
6,
127-131.
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PDB codes:
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J.L.Pellequer,
S.Chen,
V.A.Roberts,
J.A.Tainer,
and
E.D.Getzoff
(1999).
Unraveling the effect of changes in conformation and compactness at the antibody V(L)-V(H) interface upon antigen binding.
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J Mol Recognit,
12,
267-275.
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M.Scarsi,
N.Majeux,
and
A.Caflisch
(1999).
Hydrophobicity at the surface of proteins.
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Proteins,
37,
565-575.
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R.D.Stigler,
B.Hoffmann,
R.Abagyan,
and
J.Schneider-Mergener
(1999).
Soft docking an L and a D peptide to an anticholera toxin antibody using internal coordinate mechanics.
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Structure,
7,
663-670.
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R.Stanfield,
E.Cabezas,
A.Satterthwait,
E.Stura,
A.Profy,
and
I.Wilson
(1999).
Dual conformations for the HIV-1 gp120 V3 loop in complexes with different neutralizing fabs.
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Structure,
7,
131-142.
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PDB codes:
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A.Heine,
E.A.Stura,
J.T.Yli-Kauhaluoma,
C.Gao,
Q.Deng,
B.R.Beno,
K.N.Houk,
K.D.Janda,
and
I.A.Wilson
(1998).
An antibody exo Diels-Alderase inhibitor complex at 1.95 angstrom resolution.
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Science,
279,
1934-1940.
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PDB code:
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F.E.Romesberg,
B.Spiller,
P.G.Schultz,
and
R.C.Stevens
(1998).
Immunological origins of binding and catalysis in a Diels-Alderase antibody.
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Science,
279,
1929-1933.
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PDB codes:
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P.Chames,
and
D.Baty
(1998).
Engineering of an anti-steroid antibody: amino acid substitutions change antibody fine specificity from cortisol to estradiol.
|
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Clin Chem Lab Med,
36,
355-359.
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X.D.Su,
L.N.Gastinel,
D.E.Vaughn,
I.Faye,
P.Poon,
and
P.J.Bjorkman
(1998).
Crystal structure of hemolin: a horseshoe shape with implications for homophilic adhesion.
|
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Science,
281,
991-995.
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PDB code:
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C.F.Barbas,
A.Heine,
G.Zhong,
T.Hoffmann,
S.Gramatikova,
R.Björnestedt,
B.List,
J.Anderson,
E.A.Stura,
I.A.Wilson,
and
R.A.Lerner
(1997).
Immune versus natural selection: antibody aldolases with enzymic rates but broader scope.
|
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Science,
278,
2085-2092.
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PDB code:
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C.H.Trinh,
S.D.Hemmington,
M.E.Verhoeyen,
and
S.E.Phillips
(1997).
Antibody fragment Fv4155 bound to two closely related steroid hormones: the structural basis of fine specificity.
|
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Structure,
5,
937-948.
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PDB codes:
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I.A.Wilson,
and
K.C.Garcia
(1997).
T-cell receptor structure and TCR complexes.
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Curr Opin Struct Biol,
7,
839-848.
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J.L.Pellequer,
and
S.W.Chen
(1997).
Does conformational free energy distinguish loop conformations in proteins?
|
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Biophys J,
73,
2359-2375.
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M.He,
and
M.J.Taussig
(1997).
Antibody-ribosome-mRNA (ARM) complexes as efficient selection particles for in vitro display and evolution of antibody combining sites.
|
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Nucleic Acids Res,
25,
5132-5134.
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A.Pope,
K.Pritchard,
A.Williams,
A.Roberts,
J.R.Hackett,
W.Mandecki,
and
K.S.Johnson
(1996).
In vitro selection of a high affinity antibody to oestradiol using a phage display human antibody library.
|
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Immunotechnology,
2,
209-217.
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C.J.Tsai,
S.L.Lin,
H.J.Wolfson,
and
R.Nussinov
(1996).
Protein-protein interfaces: architectures and interactions in protein-protein interfaces and in protein cores. Their similarities and differences.
|
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Crit Rev Biochem Mol Biol,
31,
127-152.
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D.M.van Aalten,
R.Bywater,
J.B.Findlay,
M.Hendlich,
R.W.Hooft,
and
G.Vriend
(1996).
PRODRG, a program for generating molecular topologies and unique molecular descriptors from coordinates of small molecules.
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J Comput Aided Mol Des,
10,
255-262.
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M.Stoppini,
V.Bellotti,
A.Negri,
G.Merlini,
F.Garver,
and
G.Ferri
(1995).
Characterization of the two unique human anti-flavin monoclonal immunoglobulins.
|
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Eur J Biochem,
228,
886-893.
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M.W.Wien,
D.J.Filman,
E.A.Stura,
S.Guillot,
F.Delpeyroux,
R.Crainic,
and
J.M.Hogle
(1995).
Structure of the complex between the Fab fragment of a neutralizing antibody for type 1 poliovirus and its viral epitope.
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Nat Struct Biol,
2,
232-243.
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PDB code:
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P.M.Tang,
L.A.Foltz,
W.C.Mahoney,
and
P.A.Schueler
(1995).
A high affinity digoxin-binding protein displayed on M13 is functionally identical to the native protein.
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J Biol Chem,
270,
7829-7835.
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I.A.Wilson,
and
R.L.Stanfield
(1994).
Antibody-antigen interactions: new structures and new conformational changes.
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Curr Opin Struct Biol,
4,
857-867.
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J.F.Schildbach,
S.Y.Shaw,
R.E.Bruccoleri,
E.Haber,
L.A.Herzenberg,
G.C.Jager,
P.D.Jeffrey,
D.J.Panka,
D.R.Parks,
and
R.I.Near
(1994).
Contribution of a single heavy chain residue to specificity of an anti-digoxin monoclonal antibody.
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Protein Sci,
3,
737-749.
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J.N.Herron,
A.H.Terry,
S.Johnston,
X.M.He,
L.W.Guddat,
E.W.Voss,
and
A.B.Edmundson
(1994).
High resolution structures of the 4-4-20 Fab-fluorescein complex in two solvent systems: effects of solvent on structure and antigen-binding affinity.
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Biophys J,
67,
2167-2183.
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R.L.Malby,
W.R.Tulip,
V.R.Harley,
J.L.McKimm-Breschkin,
W.G.Laver,
R.G.Webster,
and
P.M.Colman
(1994).
The structure of a complex between the NC10 antibody and influenza virus neuraminidase and comparison with the overlapping binding site of the NC41 antibody.
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Structure,
2,
733-746.
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PDB code:
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R.L.Stanfield,
and
I.A.Wilson
(1994).
Antigen-induced conformational changes in antibodies: a problem for structural prediction and design.
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Trends Biotechnol,
12,
275-279.
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R.L.Stanfield,
M.Takimoto-Kamimura,
J.M.Rini,
A.T.Profy,
and
I.A.Wilson
(1993).
Major antigen-induced domain rearrangements in an antibody.
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Structure,
1,
83-93.
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PDB codes:
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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
