1X7B

CRYSTAL STRUCTURE OF ESTROGEN RECEPTOR BETA COMPLEXED WITH ERB-041

Summary for 1X7B

• Entry DOI: 10.2210/pdb1x7b/pdb
• Related: 1U3Q 1U3R 1U3S 1U9E 1X76 1X78 1X7J 1X7R
• Descriptor: Estrogen receptor beta, STEROID RECEPTOR COACTIVATOR-1, 2-(3-FLUORO-4-HYDROXYPHENYL)-7-VINYL-1,3-BENZOXAZOL-5-OL, ... (4 entities in total)
• Functional Keywords: estrogen receptor, estrogen receptor beta, er-beta, er, estrogen, nuclear receptor, transcription factor, agonist, transcription
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: Q92731
• Total number of polymer chains: 4
• Total formula weight: 57533.96

Authors

Manas, E.S.,Unwalla, R.J.,Xu, Z.B.,Malamas, M.S.,Miller, C.P.,Harris, H.A.,Hsiao, C.,Akopian, T.,Hum, W.T.,Malakian, K.,Wolfrom, S.,Bapat, A.,Bhat, R.A.,Stahl, M.L.,Somers, W.S.,Alvarez, J.C. (deposition date: 2004-08-13, release date: 2005-03-01, Last modification date: 2024-04-03)

Primary citation

Manas, E.S.,Unwalla, R.J.,Xu, Z.B.,Malamas, M.S.,Miller, C.P.,Harris, H.A.,Hsiao, C.,Akopian, T.,Hum, W.T.,Malakian, K.,Wolfrom, S.,Bapat, A.,Bhat, R.A.,Stahl, M.L.,Somers, W.S.,Alvarez, J.C.
Structure-Based Design of Estrogen Receptor-Beta Selective Ligands
J.Am.Chem.Soc., 126:15106-15119, 2004

PubMed Abstract: 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.

PubMed: 15548008
DOI: 10.1021/ja047633o

Experimental method

X-RAY DIFFRACTION (2.3 Å)