1h9u: Difference between revisions
From Proteopedia
Jump to navigationJump to search
No edit summary |
No edit summary |
||
| Line 5: | Line 5: | ||
==Overview== | ==Overview== | ||
Ligands that specifically target retinoid-X receptors (RXRs) are emerging, as potentially powerful therapies for cancer, diabetes, and the lowering, of circulatory cholesterol. To date, RXR has only been crystallized in the, absence of ligand or with the promiscuous ligand 9-cis retinoic acid, which also activates retinoic acid receptors. Here we present the, structure of hRXRbeta in complex with the RXR-specific agonist LG100268, (LG268). The structure clearly reveals why LG268 is specific for the RXR, ligand binding pocket and will not activate retinoic acid receptors., Intriguingly, in the crystals, the C-terminal "activation" helix, (AF-2/helix H12) is trapped in a novel position not seen in other nuclear, receptor structures such that it does not cap the ligand binding cavity., .. | Ligands that specifically target retinoid-X receptors (RXRs) are emerging, as potentially powerful therapies for cancer, diabetes, and the lowering, of circulatory cholesterol. To date, RXR has only been crystallized in the, absence of ligand or with the promiscuous ligand 9-cis retinoic acid, which also activates retinoic acid receptors. Here we present the, structure of hRXRbeta in complex with the RXR-specific agonist LG100268, (LG268). The structure clearly reveals why LG268 is specific for the RXR, ligand binding pocket and will not activate retinoic acid receptors., Intriguingly, in the crystals, the C-terminal "activation" helix, (AF-2/helix H12) is trapped in a novel position not seen in other nuclear, receptor structures such that it does not cap the ligand binding cavity., Mammalian two-hybrid assays indicate that LG268 is unable to release, co-repressors from RXR unless co-activators are also present. Together, these findings suggest that RXR ligands may be inefficient at, repositioning helix H12. | ||
==About this Structure== | ==About this Structure== | ||
1H9U is a | 1H9U 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 NI, CL and LG2 as [http://en.wikipedia.org/wiki/ligands ligands]. Structure known Active Site: LGA. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1H9U OCA]. | ||
==Reference== | ==Reference== | ||
| Line 24: | Line 24: | ||
[[Category: transcription factor]] | [[Category: transcription factor]] | ||
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 15:24:22 2007'' | ||
