1x7e
CRYSTAL STRUCTURE OF ESTROGEN RECEPTOR ALPHA COMPLEXED WITH WAY-244
OverviewOverview
We present the structure-based optimization of a series of estrogen receptor-beta (ERbeta) selective ligands. X-ray cocrystal structures of these ligands complexed to both ERalpha and ERbeta are described. We also discuss how molecular modeling was used to take advantage of subtle differences between the two binding cavities in order to optimize selectivity for ERbeta over ERalpha. Quantum chemical calculations are utilized to gain insight into the mechanism of selectivity enhancement. Despite only two relatively conservative residue substitutions in the ligand binding pocket, the most selective compounds have greater than 100-fold selectivity for ERbeta relative to ERalpha when measured using a competitive radioligand binding assay.
About this StructureAbout this Structure
1X7E is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Structure-based design of estrogen receptor-beta selective ligands., Manas ES, Unwalla RJ, Xu ZB, Malamas MS, Miller CP, Harris HA, Hsiao C, Akopian T, Hum WT, Malakian K, Wolfrom S, Bapat A, Bhat RA, Stahl ML, Somers WS, Alvarez JC, J Am Chem Soc. 2004 Nov 24;126(46):15106-19. PMID:15548008 Page seeded by OCA on Sat May 3 14:39:44 2008
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OCA- Pages with broken file links
- Homo sapiens
- Single protein
- Akopian, T.
- Alvarez, J C.
- Bapat, A.
- Bhat, R A.
- Harris, H A.
- Hsiao, C.
- Hum, W T.
- Malakian, K.
- Malamas, M S.
- Manas, E S.
- Miller, C P.
- Somers, W S.
- Stahl, M L.
- Unwalla, R J.
- Wolfrom, S.
- Xu, Z B.
- Agonist
- Er
- Er-alpha
- Er-beta
- Estrogen
- Estrogen receptor
- Estrogen receptor alpha
- Estrogen receptor beta
- Nuclear recept transcription factor