1xap
From Proteopedia
(New page: 200px<br /> <applet load="1xap" size="450" color="white" frame="true" align="right" spinBox="true" caption="1xap, resolution 2.1Å" /> '''Structure of the lig...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1xap. | + | [[Image:1xap.jpg|left|200px]]<br /><applet load="1xap" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1xap" size=" | + | |
caption="1xap, resolution 2.1Å" /> | caption="1xap, resolution 2.1Å" /> | ||
'''Structure of the ligand binding domain of the Retinoic Acid Receptor beta'''<br /> | '''Structure of the ligand binding domain of the Retinoic Acid Receptor beta'''<br /> | ||
| Line 11: | Line 10: | ||
==About this Structure== | ==About this Structure== | ||
| - | 1XAP 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 TTB as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1XAP 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=TTB:'>TTB</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XAP OCA]. |
==Reference== | ==Reference== | ||
| Line 35: | Line 34: | ||
[[Category: ttnpb]] | [[Category: ttnpb]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 17:08:41 2008'' |
Revision as of 15:08, 15 February 2008
|
Structure of the ligand binding domain of the Retinoic Acid Receptor beta
Contents |
Overview
The crystal structure of the ligand-binding domain of RARbeta, a suspect, tumour suppressor, reveals important features that distinguish it from the, two other RAR isotypes. The most striking difference is an extra cavity, allowing RARbeta to bind more bulky agonists. Accordingly, we identified a, ligand that shows RARbeta selectivity with a 100-fold higher affinity to, RARbeta than to alpha or gamma isotypes. The structural differences, between the three RAR ligand-binding pockets revealed a rationale, explaining how a single retinoid can be at the same time an RARalpha, gamma antagonist and an RARbeta agonist. In addition, we demonstrate how, to generate an RARbeta antagonist by gradually modifying the bulkiness of, a single substitution. Together, our results provide structural guidelines, for the synthesis of RARbeta-selective agonists and antagonists, allowing, for the first time to address pharmacologically the tumour suppressor role, of RARbeta in vitro and in animal models.
Disease
Known disease associated with this structure: Camptodactyly-arthropathy-coxa vara-pericarditis syndrome OMIM:[604283]
About this Structure
1XAP is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
Reference
Rational design of RAR-selective ligands revealed by RARbeta crystal stucture., Germain P, Kammerer S, Perez E, Peluso-Iltis C, Tortolani D, Zusi FC, Starrett J, Lapointe P, Daris JP, Marinier A, de Lera AR, Rochel N, Gronemeyer H, EMBO Rep. 2004 Sep;5(9):877-82. PMID:15319780
Page seeded by OCA on Fri Feb 15 17:08:41 2008
Categories: Homo sapiens | Single protein | Daris, J.P. | Germain, P. | Gronemeyer, H. | Kammerer, S. | Lapointe, P. | Lera, A.R.De. | Marinier, A. | Peluso-Iltis, C. | Rochel, N. | Starrett, J. | Tortolani, D. | Zusi, F.C. | TTB | Ligand binding domain | Nuclear receptor | Retinoic acid receptor beta | Ttnpb
