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1xap
From Proteopedia
| 1xap, resolution 2.10Å () | |||||||||
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| Ligands: | |||||||||
| Domains: | Hormone_recep | ||||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
Structure of the ligand binding domain of the Retinoic Acid Receptor beta
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.
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
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
1XAP is a 1 chain structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
- 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. Rational design of RAR-selective ligands revealed by RARbeta crystal stucture. EMBO Rep. 2004 Sep;5(9):877-82. PMID:15319780 doi:10.1038/sj.embor.7400235
Page seeded by OCA on Tue Feb 17 16:37:33 2009
