1u3s: Difference between revisions
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'''Crystal Structure of Estrogen Receptor beta complexed with WAY-797''' | {{Structure | ||
|PDB= 1u3s |SIZE=350|CAPTION= <scene name='initialview01'>1u3s</scene>, resolution 2.50Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=797:3-(6-HYDROXY-NAPHTHALEN-2-YL)-BENZO[D]ISOOXAZOL-6-OL'>797</scene> | |||
|ACTIVITY= | |||
|GENE= ESR2, NR3A2, ESTRB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |||
}} | |||
'''Crystal Structure of Estrogen Receptor beta complexed with WAY-797''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1U3S is a [ | 1U3S is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1U3S OCA]. | ||
==Reference== | ==Reference== | ||
Design and synthesis of aryl diphenolic azoles as potent and selective estrogen receptor-beta ligands., Malamas MS, Manas ES, McDevitt RE, Gunawan I, Xu ZB, Collini MD, Miller CP, Dinh T, Henderson RA, Keith JC Jr, Harris HA, J Med Chem. 2004 Oct 7;47(21):5021-40. PMID:[http:// | Design and synthesis of aryl diphenolic azoles as potent and selective estrogen receptor-beta ligands., Malamas MS, Manas ES, McDevitt RE, Gunawan I, Xu ZB, Collini MD, Miller CP, Dinh T, Henderson RA, Keith JC Jr, Harris HA, J Med Chem. 2004 Oct 7;47(21):5021-40. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15456246 15456246] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: transcription factor]] | [[Category: transcription factor]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:27:01 2008'' | ||
Revision as of 15:27, 20 March 2008
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| , resolution 2.50Å | |||||||
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| Ligands: | |||||||
| Gene: | ESR2, NR3A2, ESTRB (Homo sapiens) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure of Estrogen Receptor beta complexed with WAY-797
OverviewOverview
New diphenolic azoles as highly selective estrogen receptor-beta agonists are reported. The more potent and selective analogues of these series have comparable binding affinities for ERbeta as the natural ligand 17beta-estradiol but are >100-fold selective over ERalpha. Our design strategy not only followed a traditional SAR approach but also was supported by X-ray structures of ERbeta cocrystallized with various ligands as well as molecular modeling studies. These strategies enabled us to take advantage of a single conservative residue substitution in the ligand-binding pocket, ERalpha Met(421) --> ERbeta Ile(373), to optimize ERbeta selectivity. The 7-position-substituted benzoxazoles (Table 5) were the most selective ligands of both azole series, with ERB-041 (117) being >200-fold selective for ERbeta. The majority of ERbeta selective agonists tested that were at least approximately 50-fold selective displayed a consistent in vivo profile: they were inactive in several models of classic estrogen action (uterotrophic, osteopenia, and vasomotor instability models) and yet were active in the HLA-B27 transgenic rat model of inflammatory bowel disease. These data suggest that ERbeta-selective agonists are devoid of classic estrogenic effects and may offer a novel therapy to treat certain inflammatory conditions.
About this StructureAbout this Structure
1U3S is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Design and synthesis of aryl diphenolic azoles as potent and selective estrogen receptor-beta ligands., Malamas MS, Manas ES, McDevitt RE, Gunawan I, Xu ZB, Collini MD, Miller CP, Dinh T, Henderson RA, Keith JC Jr, Harris HA, J Med Chem. 2004 Oct 7;47(21):5021-40. PMID:15456246
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