1u3r

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spinqualitylabelsall models PDB ID 1u3r Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image
, resolution 2.21Å
Ligands:
Gene:	ESR2, NR3A2, ESTRB (Homo sapiens)
Related:	1U3Q, 1U3S
Resources:	FirstGlance, OCA, PDBsum, RCSB
Coordinates:	save as pdb, mmCIF, xml

Crystal Structure of Estrogen Receptor beta complexed with WAY-338

Overview

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 Structure

1U3R is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

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:15456246

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