1u9e: Difference between revisions

[[Image:1u9e.gif|left|200px]]<br /><applet load="1u9e" size="350" color="white" frame="true" align="right" spinBox="true"  

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.

1U9E is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=397:'>397</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1U9E OCA].  

[[Category: Alvarez, J C.]]

[[Category: Bhat, R A.]]

[[Category: Harris, H A.]]

[[Category: Hum, W T.]]

[[Category: Malamas, M S.]]

[[Category: Manas, E S.]]

[[Category: Miller, C P.]]

[[Category: Somers, W S.]]

[[Category: Stahl, M L.]]

[[Category: Unwalla, R J.]]

[[Category: Xu, Z B.]]

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