1p8d

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spinqualitylabelsall models 1p8d, resolution 2.8Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

X-Ray Crystal Structure of LXR Ligand Binding Domain with 24(S),25-epoxycholesterol

Overview

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 Structure

1P8D is a Protein complex structure of sequences from Homo sapiens with CO1 as ligand. Full crystallographic information is available from OCA.

Reference

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 Mon Nov 12 18:40:55 2007