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PDBsum entry 1yy4
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Transcription
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PDB id
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1yy4
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Contents |
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* Residue conservation analysis
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PDB id:
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| Name: |
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Transcription
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Title:
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Crystal structure of estrogen receptor beta complexed with 1-chloro-6- (4-hydroxy-phenyl)-naphthalen-2-ol
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Structure:
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Estrogen receptor beta. Chain: a, b. Fragment: ligand binding domain. Synonym: er-beta. Engineered: yes. Steroid receptor coactivator-1. Chain: c, d. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: esr2, estrb, nr3a2. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes. Other_details: this sequence was derived from steroid receptor coactivator-1
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Biol. unit:
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Tetramer (from
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Resolution:
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2.70Å
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R-factor:
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0.214
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R-free:
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0.269
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Authors:
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R.E.Mewshaw,R.J.Edsall Jr.,C.Yang,E.S.Manas,Z.B.Xu,R.A.Henderson, J.C.Keith Jr.,H.A.Harris
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Key ref:
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R.E.Mewshaw
et al.
(2005).
ERbeta ligands. 3. Exploiting two binding orientations of the 2-phenylnaphthalene scaffold to achieve ERbeta selectivity.
J Med Chem,
48,
3953-3979.
PubMed id:
DOI:
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Date:
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23-Feb-05
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Release date:
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28-Feb-06
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PROCHECK
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Headers
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References
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Q92731
(ESR2_HUMAN) -
Estrogen receptor beta from Homo sapiens
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Seq:
Struc:
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530 a.a.
225 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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DOI no:
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J Med Chem
48:3953-3979
(2005)
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PubMed id:
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ERbeta ligands. 3. Exploiting two binding orientations of the 2-phenylnaphthalene scaffold to achieve ERbeta selectivity.
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R.E.Mewshaw,
R.J.Edsall,
C.Yang,
E.S.Manas,
Z.B.Xu,
R.A.Henderson,
J.C.Keith,
H.A.Harris.
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ABSTRACT
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The 2-phenylnaphthalene scaffold was explored as a simplified version of
genistein in order to identify ER selective ligands. With the aid of docking
studies, positions 1, 4, and 8 of the 2-phenylnaphthalene template were
predicted to be the most potentially influential positions to enhance ER
selectivity using two different binding orientations. Both orientations have the
phenol moiety mimicking the A-ring of genistein. Several compounds predicted to
adopt orientations similar to that of genistein when bound to ERbeta were
observed to have slightly higher ER affinity and selectivity than genistein. The
second orientation we exploited, which was different from that of genistein when
bound to ERbeta, resulted in the discovery of several compounds that had
superior ER selectivity and affinity versus genistein. X-ray structures of two
ER selective compounds (i.e., 15 and 47) confirmed the alternate binding mode
and suggested that substituents at positions 1 and 8 were responsible for
inducing selectivity. One compound (i.e., 47, WAY-202196) was further examined
and found to be effective in two models of inflammation, suggesting that
targeting ER may be therapeutically useful in treating certain chronic
inflammatory diseases.
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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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F.Minutolo,
M.Macchia,
B.S.Katzenellenbogen,
and
J.A.Katzenellenbogen
(2011).
Estrogen receptor β ligands: Recent advances and biomedical applications.
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Med Res Rev,
31,
364-442.
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Z.Wang,
Y.Li,
C.Ai,
and
Y.Wang
(2010).
In silico prediction of estrogen receptor subtype binding affinity and selectivity using statistical methods and molecular docking with 2-arylnaphthalenes and 2-arylquinolines.
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Int J Mol Sci,
11,
3434-3458.
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D.L.Mobley,
and
K.A.Dill
(2009).
Binding of small-molecule ligands to proteins: "what you see" is not always "what you get".
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Structure,
17,
489-498.
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R.Kennelly,
D.O.Kavanagh,
A.M.Hogan,
and
D.C.Winter
(2008).
Oestrogen and the colon: potential mechanisms for cancer prevention.
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Lancet Oncol,
9,
385-391.
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H.A.Harris
(2006).
The unexpected science of estrogen receptor-beta selective agonists: a new class of anti-inflammatory agents?
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Nucl Recept Signal,
4,
e012.
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P.A.Cristofaro,
S.M.Opal,
J.E.Palardy,
N.A.Parejo,
J.Jhung,
J.C.Keith,
and
H.A.Harris
(2006).
WAY-202196, a selective estrogen receptor-beta agonist, protects against death in experimental septic shock.
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Crit Care Med,
34,
2188-2193.
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P.Ascenzi,
A.Bocedi,
and
M.Marino
(2006).
Structure-function relationship of estrogen receptor alpha and beta: impact on human health.
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Mol Aspects Med,
27,
299-402.
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R.W.Hsieh,
S.S.Rajan,
S.K.Sharma,
Y.Guo,
E.R.DeSombre,
M.Mrksich,
and
G.L.Greene
(2006).
Identification of ligands with bicyclic scaffolds provides insights into mechanisms of estrogen receptor subtype selectivity.
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J Biol Chem,
281,
17909-17919.
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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
codes are
shown on the right.
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Links
