1p93
From Proteopedia
(New page: 200px<br /> <applet load="1p93" size="450" color="white" frame="true" align="right" spinBox="true" caption="1p93, resolution 2.70Å" /> '''CRYSTAL STRUCTURE O...) |
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| - | [[Image:1p93.gif|left|200px]]<br /> | + | [[Image:1p93.gif|left|200px]]<br /><applet load="1p93" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1p93" size=" | + | |
caption="1p93, resolution 2.70Å" /> | caption="1p93, resolution 2.70Å" /> | ||
'''CRYSTAL STRUCTURE OF THE AGONIST FORM OF GLUCOCORTICOID RECEPTOR'''<br /> | '''CRYSTAL STRUCTURE OF THE AGONIST FORM OF GLUCOCORTICOID RECEPTOR'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Here we describe the three-dimensional crystal structures of human | + | Here we describe the three-dimensional crystal structures of human glucocorticoid receptor ligand-binding domain (GR-LBD) in complex with the antagonist RU-486 at 2.3 A resolution and with the agonist dexamethasone ligand together with a coactivator peptide at 2.8 A. The RU-486 structure was solved in several different crystal forms, two with helix 12 intact (GR1 and GR3) and one with a protease-digested C terminus (GR2). In GR1, part of helix 12 is in a position that covers the co-activator pocket, whereas in the GR3, domain swapping is seen between the crystallographically identical subunits in the GR dimer. An arm consisting of the end of helix 11 and beyond stretches out from one molecule, and helix 12 binds to the other LBD, partly blocking the coactivator pocket of that molecule. This type of GR-LBD dimer has not been described before but might be an artifact from crystallization. Furthermore, the subunits of the GR3 dimers are covalently connected via a disulfide bond between the Cys-736 residues in the two molecules. All three RU-486 GR-LBD structures show that GR has a very flexible region between the end of helix 11 and the end of helix 12. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1P93 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with DEX as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1P93 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=DEX:'>DEX</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1P93 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Farnegardh, M.]] | [[Category: Farnegardh, M.]] | ||
[[Category: Greer, J.]] | [[Category: Greer, J.]] | ||
| - | [[Category: Gustafsson, J | + | [[Category: Gustafsson, J A.]] |
[[Category: Harlan, J.]] | [[Category: Harlan, J.]] | ||
[[Category: Jakob, C.]] | [[Category: Jakob, C.]] | ||
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[[Category: Muchmore, S.]] | [[Category: Muchmore, S.]] | ||
[[Category: Ohman, L.]] | [[Category: Ohman, L.]] | ||
| - | [[Category: Ramqvist, A | + | [[Category: Ramqvist, A K.]] |
[[Category: Thorell, S.]] | [[Category: Thorell, S.]] | ||
[[Category: Yang, J.]] | [[Category: Yang, J.]] | ||
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[[Category: protien-ligand complex]] | [[Category: protien-ligand complex]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:26:25 2008'' |
Revision as of 12:26, 21 February 2008
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CRYSTAL STRUCTURE OF THE AGONIST FORM OF GLUCOCORTICOID RECEPTOR
Contents |
Overview
Here we describe the three-dimensional crystal structures of human glucocorticoid receptor ligand-binding domain (GR-LBD) in complex with the antagonist RU-486 at 2.3 A resolution and with the agonist dexamethasone ligand together with a coactivator peptide at 2.8 A. The RU-486 structure was solved in several different crystal forms, two with helix 12 intact (GR1 and GR3) and one with a protease-digested C terminus (GR2). In GR1, part of helix 12 is in a position that covers the co-activator pocket, whereas in the GR3, domain swapping is seen between the crystallographically identical subunits in the GR dimer. An arm consisting of the end of helix 11 and beyond stretches out from one molecule, and helix 12 binds to the other LBD, partly blocking the coactivator pocket of that molecule. This type of GR-LBD dimer has not been described before but might be an artifact from crystallization. Furthermore, the subunits of the GR3 dimers are covalently connected via a disulfide bond between the Cys-736 residues in the two molecules. All three RU-486 GR-LBD structures show that GR has a very flexible region between the end of helix 11 and the end of helix 12.
Disease
Known diseases associated with this structure: Cortisol resistance OMIM:[138040]
About this Structure
1P93 is a Protein complex structure of sequences from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
Reference
The three-dimensional structures of antagonistic and agonistic forms of the glucocorticoid receptor ligand-binding domain: RU-486 induces a transconformation that leads to active antagonism., Kauppi B, Jakob C, Farnegardh M, Yang J, Ahola H, Alarcon M, Calles K, Engstrom O, Harlan J, Muchmore S, Ramqvist AK, Thorell S, Ohman L, Greer J, Gustafsson JA, Carlstedt-Duke J, Carlquist M, J Biol Chem. 2003 Jun 20;278(25):22748-54. Epub 2003 Apr 9. PMID:12686538
Page seeded by OCA on Thu Feb 21 14:26:25 2008
Categories: Homo sapiens | Protein complex | Ahola, H. | Alarcon, M. | Calles, K. | Carlquist, M. | Carlstedt-Duke, J. | Engstrom, O. | Farnegardh, M. | Greer, J. | Gustafsson, J A. | Harlan, J. | Jakob, C. | Kauppi, B. | Muchmore, S. | Ohman, L. | Ramqvist, A K. | Thorell, S. | Yang, J. | DEX | Anti parallel alpha helix sandwich | Protien-ligand complex
