1x7e
From Proteopedia
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|ACTIVITY= | |ACTIVITY= | ||
|GENE= ESR1, NR3A1, ESR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= ESR1, NR3A1, ESR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1u3q|1U3Q]], [[1u3r|1U3R]], [[1u3s|1U3S]], [[1u9e|1U9E]], [[1x76|1X76]], [[1x78|1X78]], [[1x7b|1X7B]], [[1x7d|1X7D]], [[1x7j|1X7J]], [[1x7r|1X7R]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1x7e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1x7e OCA], [http://www.ebi.ac.uk/pdbsum/1x7e PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1x7e RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==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. | 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. | ||
| - | |||
| - | ==Disease== | ||
| - | Known diseases associated with this structure: Atherosclerosis, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=133430 133430]], Breast cancer OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=133430 133430]], Estrogen resistance OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=133430 133430]], HDL response to hormone replacement, augmented OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=133430 133430]], Migraine, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=133430 133430]], Myocardial infarction, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=133430 133430]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Wolfrom, S.]] | [[Category: Wolfrom, S.]] | ||
[[Category: Xu, Z B.]] | [[Category: Xu, Z B.]] | ||
| - | [[Category: 244]] | ||
[[Category: agonist]] | [[Category: agonist]] | ||
[[Category: er]] | [[Category: er]] | ||
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[[Category: nuclear recept transcription factor]] | [[Category: nuclear recept transcription factor]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:45:40 2008'' |
Revision as of 21:45, 30 March 2008
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| , resolution 2.80Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | ESR1, NR3A1, ESR (Homo sapiens) | ||||||
| Related: | 1U3Q, 1U3R, 1U3S, 1U9E, 1X76, 1X78, 1X7B, 1X7D, 1X7J, 1X7R
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CRYSTAL STRUCTURE OF ESTROGEN RECEPTOR ALPHA COMPLEXED WITH WAY-244
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
1X7E is a Single protein structure of sequence from Homo sapiens. 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 Mon Mar 31 00:45:40 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. | Agonist | Er | Er-alpha | Er-beta | Estrogen | Estrogen receptor | Estrogen receptor alpha | Estrogen receptor beta | Nuclear recept transcription factor
