2qe4: Difference between revisions
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==Overview== | ==Overview== | ||
Benzopyrans are selective estrogen receptor (ER) beta agonists (SERBAs), which bind the ER receptor subtypes alpha and beta in opposite | Benzopyrans are selective estrogen receptor (ER) beta agonists (SERBAs), which bind the ER receptor subtypes alpha and beta in opposite orientations. We have used structure based drug design to show that this unique phenomena can be exploited via substitution at the 8-position of the benzopyran A-ring to disrupt binding to ERalpha, thus improving ERbeta subtype selectivity. X-ray cocrystal structures with ERalpha and ERbeta are supportive of this approach to improve selectivity in this structural class. | ||
==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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==Reference== | ==Reference== | ||
Benzopyrans as selective estrogen receptor beta agonists (SERBAs). Part 4: | Benzopyrans as selective estrogen receptor beta agonists (SERBAs). Part 4: functionalization of the benzopyran A-ring., Norman BH, Richardson TI, Dodge JA, Pfeifer LA, Durst GL, Wang Y, Durbin JD, Krishnan V, Dinn SR, Liu S, Reilly JE, Ryter KT, Bioorg Med Chem Lett. 2007 Sep 15;17(18):5082-5. Epub 2007 Jul 13. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17662603 17662603] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Dinn, S | [[Category: Dinn, S R.]] | ||
[[Category: Dodge, J | [[Category: Dodge, J A.]] | ||
[[Category: Durbin, J | [[Category: Durbin, J D.]] | ||
[[Category: Durst, G | [[Category: Durst, G L.]] | ||
[[Category: Krishnan, V.]] | [[Category: Krishnan, V.]] | ||
[[Category: Liu, S | [[Category: Liu, S Q.]] | ||
[[Category: Norman, B | [[Category: Norman, B H.]] | ||
[[Category: Pfeifer, L | [[Category: Pfeifer, L A.]] | ||
[[Category: Reilly, J | [[Category: Reilly, J E.]] | ||
[[Category: Richardson, T | [[Category: Richardson, T I.]] | ||
[[Category: Ryter, K | [[Category: Ryter, K T.]] | ||
[[Category: Wang, Y.]] | [[Category: Wang, Y.]] | ||
[[Category: JJ3]] | [[Category: JJ3]] | ||
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[[Category: zinc-finger]] | [[Category: zinc-finger]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:38:29 2008'' | ||
Revision as of 19:38, 21 February 2008
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Estrogen receptor alpha ligand-binding domain in complex with a benzopyran agonist
OverviewOverview
Benzopyrans are selective estrogen receptor (ER) beta agonists (SERBAs), which bind the ER receptor subtypes alpha and beta in opposite orientations. We have used structure based drug design to show that this unique phenomena can be exploited via substitution at the 8-position of the benzopyran A-ring to disrupt binding to ERalpha, thus improving ERbeta subtype selectivity. X-ray cocrystal structures with ERalpha and ERbeta are supportive of this approach to improve selectivity in this structural class.
DiseaseDisease
Known diseases associated with this structure: Atherosclerosis, susceptibility to OMIM:[133430], Breast cancer OMIM:[133430], Estrogen resistance OMIM:[133430], HDL response to hormone replacement, augmented OMIM:[133430], Migraine, susceptibility to OMIM:[133430], Myocardial infarction, susceptibility to OMIM:[133430]
About this StructureAbout this Structure
2QE4 is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
ReferenceReference
Benzopyrans as selective estrogen receptor beta agonists (SERBAs). Part 4: functionalization of the benzopyran A-ring., Norman BH, Richardson TI, Dodge JA, Pfeifer LA, Durst GL, Wang Y, Durbin JD, Krishnan V, Dinn SR, Liu S, Reilly JE, Ryter KT, Bioorg Med Chem Lett. 2007 Sep 15;17(18):5082-5. Epub 2007 Jul 13. PMID:17662603
Page seeded by OCA on Thu Feb 21 18:38:29 2008
Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)
OCA- Pages with broken file links
- Homo sapiens
- Single protein
- Dinn, S R.
- Dodge, J A.
- Durbin, J D.
- Durst, G L.
- Krishnan, V.
- Liu, S Q.
- Norman, B H.
- Pfeifer, L A.
- Reilly, J E.
- Richardson, T I.
- Ryter, K T.
- Wang, Y.
- JJ3
- Alternative splicing
- Dna-binding
- Ligand-binding domain
- Lipid-binding
- Metal-binding
- Nuclear protein
- Nuclear receptor
- Phosphorylation
- Polymorphism
- Steroid-binding
- Transcription
- Transcription regulation
- Zinc
- Zinc-finger