1x7b
From Proteopedia
(New page: 200px<br /> <applet load="1x7b" size="450" color="white" frame="true" align="right" spinBox="true" caption="1x7b, resolution 2.30Å" /> '''CRYSTAL STRUCTURE O...) |
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| - | [[Image:1x7b.gif|left|200px]]<br /> | + | [[Image:1x7b.gif|left|200px]]<br /><applet load="1x7b" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1x7b" size=" | + | |
caption="1x7b, resolution 2.30Å" /> | caption="1x7b, resolution 2.30Å" /> | ||
'''CRYSTAL STRUCTURE OF ESTROGEN RECEPTOR BETA COMPLEXED WITH ERB-041'''<br /> | '''CRYSTAL STRUCTURE OF ESTROGEN RECEPTOR BETA COMPLEXED WITH ERB-041'''<br /> | ||
==Overview== | ==Overview== | ||
| - | We present the structure-based optimization of a series of estrogen | + | 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 Structure== | ==About this Structure== | ||
| - | 1X7B 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 041 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1X7B 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=041:'>041</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1X7B OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Akopian, T.]] | [[Category: Akopian, T.]] | ||
| - | [[Category: Alvarez, J | + | [[Category: Alvarez, J C.]] |
[[Category: Bapat, A.]] | [[Category: Bapat, A.]] | ||
| - | [[Category: Bhat, R | + | [[Category: Bhat, R A.]] |
| - | [[Category: Harris, H | + | [[Category: Harris, H A.]] |
[[Category: Hsiao, C.]] | [[Category: Hsiao, C.]] | ||
| - | [[Category: Hum, W | + | [[Category: Hum, W T.]] |
[[Category: Malakian, K.]] | [[Category: Malakian, K.]] | ||
| - | [[Category: Malamas, M | + | [[Category: Malamas, M S.]] |
| - | [[Category: Manas, E | + | [[Category: Manas, E S.]] |
| - | [[Category: Miller, C | + | [[Category: Miller, C P.]] |
| - | [[Category: Somers, W | + | [[Category: Somers, W S.]] |
| - | [[Category: Stahl, M | + | [[Category: Stahl, M L.]] |
| - | [[Category: Unwalla, R | + | [[Category: Unwalla, R J.]] |
[[Category: Wolfrom, S.]] | [[Category: Wolfrom, S.]] | ||
| - | [[Category: Xu, Z | + | [[Category: Xu, Z B.]] |
[[Category: 041]] | [[Category: 041]] | ||
[[Category: agonist]] | [[Category: agonist]] | ||
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[[Category: transcription factor]] | [[Category: transcription factor]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:51:42 2008'' |
Revision as of 13:51, 21 February 2008
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CRYSTAL STRUCTURE OF ESTROGEN RECEPTOR BETA COMPLEXED WITH ERB-041
Overview
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 Structure
1X7B is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
Reference
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 Thu Feb 21 15:51:42 2008
Categories: 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. | 041 | Agonist | Er | Er-beta | Estrogen | Estrogen receptor | Estrogen receptor beta | Nuclear receptor | Transcription factor
