1p8d
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| , resolution 2.8Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | NR1H2 OR LXRB OR UNR OR NER (Homo sapiens) | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
X-Ray Crystal Structure of LXR Ligand Binding Domain with 24(S),25-epoxycholesterol
OverviewOverview
The x-ray crystal structures of the human liver X receptor beta ligand binding domain complexed to sterol and nonsterol agonists revealed a perpendicular histidinetryptophan switch that holds the receptor in its active conformation. Hydrogen bonding interactions with the ligand act to position the His-435 imidazole ring against the Trp-457 indole ring, allowing an electrostatic interaction that holds the AF2 helix in the active position. The neutral oxysterol 24(S),25-epoxycholesterol accepts a hydrogen bond from His-435 that positions the imidazole ring of the histidine above the pyrrole ring of the tryptophan. In contrast, the acidic T0901317 hydroxyl group makes a shorter hydrogen bond with His-435 that pulls the imidazole over the electron-rich benzene ring of the tryptophan, possibly strengthening the electrostatic interaction. Point mutagenesis of Trp-457 supports the observation that the ligand-histidine-tryptophan coupling is different between the two ligands. The lipophilic liver X receptor ligand-binding pocket is larger than the corresponding steroid hormone receptors, which allows T0901317 to adopt two distinct conformations. These results provide a molecular basis for liver X receptor activation by a wide range of endogenous neutral and acidic ligands.
About this StructureAbout this Structure
1P8D is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
X-ray crystal structure of the liver X receptor beta ligand binding domain: regulation by a histidine-tryptophan switch., Williams S, Bledsoe RK, Collins JL, Boggs S, Lambert MH, Miller AB, Moore J, McKee DD, Moore L, Nichols J, Parks D, Watson M, Wisely B, Willson TM, J Biol Chem. 2003 Jul 18;278(29):27138-43. Epub 2003 May 7. PMID:12736258
Page seeded by OCA on Sun Mar 30 22:56:21 2008