2b23: Difference between revisions
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|ACTIVITY= | |ACTIVITY= | ||
|GENE= ESR1, ESR, NR3A1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= ESR1, ESR, NR3A1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
|DOMAIN= | |DOMAIN=<span class='plainlinks'>[http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=pfam00104 Hormone_recep]</span> | ||
|RELATEDENTRY=[[2b1v|2B1V]], [[2b1z|2B1Z]] | |RELATEDENTRY=[[2b1v|2B1V]], [[2b1z|2B1Z]] | ||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2b23 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2b23 OCA], [http://www.ebi.ac.uk/pdbsum/2b23 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2b23 RCSB]</span> | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2b23 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2b23 OCA], [http://www.ebi.ac.uk/pdbsum/2b23 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2b23 RCSB]</span> | ||
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'''Human estrogen receptor alpha ligand-binding domain and a glucocorticoid receptor-interacting protein 1 NR box II peptide''' | '''Human estrogen receptor alpha ligand-binding domain and a glucocorticoid receptor-interacting protein 1 NR box II peptide''' | ||
==Overview== | |||
Our understanding of how steroid hormones regulate physiological functions has been significantly advanced by structural biology approaches. However, progress has been hampered by misfolding of the ligand binding domains in heterologous expression systems and by conformational flexibility that interferes with crystallization. Here, we show that protein folding problems that are common to steroid hormone receptors are circumvented by mutations that stabilize well-characterized conformations of the receptor. We use this approach to present the structure of an apo steroid receptor that reveals a ligand-accessible channel allowing soaking of preformed crystals. Furthermore, crystallization of different pharmacological classes of compounds allowed us to define the structural basis of NFkappaB-selective signaling through the estrogen receptor, thus revealing a unique conformation of the receptor that allows selective suppression of inflammatory gene expression. The ability to crystallize many receptor-ligand complexes with distinct pharmacophores allows one to define structural features of signaling specificity that would not be apparent in a single structure. | |||
==About this Structure== | ==About this Structure== | ||
2B23 is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2B23 OCA]. | 2B23 is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2B23 OCA]. | ||
==Reference== | |||
NFkappaB selectivity of estrogen receptor ligands revealed by comparative crystallographic analyses., Nettles KW, Bruning JB, Gil G, Nowak J, Sharma SK, Hahm JB, Kulp K, Hochberg RB, Zhou H, Katzenellenbogen JA, Katzenellenbogen BS, Kim Y, Joachmiak A, Greene GL, Nat Chem Biol. 2008 Apr;4(4):241-7. Epub 2008 Mar 16. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18344977 18344977] | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
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[[Category: lbd]] | [[Category: lbd]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Apr 2 11:31:27 2008'' | ||
Revision as of 11:31, 2 April 2008
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| , resolution 2.10Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | ESR1, ESR, NR3A1 (Homo sapiens) | ||||||
| Domains: | Hormone_recep | ||||||
| Related: | 2B1V, 2B1Z
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Human estrogen receptor alpha ligand-binding domain and a glucocorticoid receptor-interacting protein 1 NR box II peptide
OverviewOverview
Our understanding of how steroid hormones regulate physiological functions has been significantly advanced by structural biology approaches. However, progress has been hampered by misfolding of the ligand binding domains in heterologous expression systems and by conformational flexibility that interferes with crystallization. Here, we show that protein folding problems that are common to steroid hormone receptors are circumvented by mutations that stabilize well-characterized conformations of the receptor. We use this approach to present the structure of an apo steroid receptor that reveals a ligand-accessible channel allowing soaking of preformed crystals. Furthermore, crystallization of different pharmacological classes of compounds allowed us to define the structural basis of NFkappaB-selective signaling through the estrogen receptor, thus revealing a unique conformation of the receptor that allows selective suppression of inflammatory gene expression. The ability to crystallize many receptor-ligand complexes with distinct pharmacophores allows one to define structural features of signaling specificity that would not be apparent in a single structure.
About this StructureAbout this Structure
2B23 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
NFkappaB selectivity of estrogen receptor ligands revealed by comparative crystallographic analyses., Nettles KW, Bruning JB, Gil G, Nowak J, Sharma SK, Hahm JB, Kulp K, Hochberg RB, Zhou H, Katzenellenbogen JA, Katzenellenbogen BS, Kim Y, Joachmiak A, Greene GL, Nat Chem Biol. 2008 Apr;4(4):241-7. Epub 2008 Mar 16. PMID:18344977
Page seeded by OCA on Wed Apr 2 11:31:27 2008