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PDBsum entry 1pq6
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protein ligands Protein-protein interface(s) links
Transcription regulation PDB id
1pq6

 

 

 

 

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Contents
Protein chains
232 a.a. *
208 a.a. *
Ligands
965 ×3
IPA ×2
Waters ×167
* Residue conservation analysis
PDB id:
1pq6
Name: Transcription regulation
Title: Human lxr beta hormone receptor / gw3965 complex
Structure: Oxysterols receptor lxr-beta. Chain: a, b, c, d. Fragment: ligand binding domain, residues 213-461. Synonym: liver x receptor beta, nuclear orphan receptor lxr-beta, ubiquitously-expressed nuclear receptor, nuclear receptor ner. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: nr1h2 or lxrb or unr or ner. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PQS)
Resolution:
2.40Å     R-factor:   0.209     R-free:   0.262
Authors: M.Farnegardh,T.Bonn,S.Sun,J.Ljunggren,H.Ahola,A.Wilhelmsson,J.- A.Gustafsson,M.Carlquist
Key ref:
M.Färnegårdh et al. (2003). The three-dimensional structure of the liver X receptor beta reveals a flexible ligand-binding pocket that can accommodate fundamentally different ligands. J Biol Chem, 278, 38821-38828. PubMed id: 12819202 DOI: 10.1074/jbc.M304842200
Date:
18-Jun-03     Release date:   09-Sep-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P55055  (NR1H2_HUMAN) -  Oxysterols receptor LXR-beta from Homo sapiens
Seq:
Struc: 		460 a.a.
232 a.a.
Protein chain
Pfam   ArchSchema ?
P55055  (NR1H2_HUMAN) -  Oxysterols receptor LXR-beta from Homo sapiens
Seq:
Struc: 		460 a.a.
208 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chains A, B, C, D: E.C.?
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

 

 
DOI no: 10.1074/jbc.M304842200 J Biol Chem 278:38821-38828 (2003)
PubMed id: 12819202  
 
 
The three-dimensional structure of the liver X receptor beta reveals a flexible ligand-binding pocket that can accommodate fundamentally different ligands.
M.Färnegårdh, T.Bonn, S.Sun, J.Ljunggren, H.Ahola, A.Wilhelmsson, J.A.Gustafsson, M.Carlquist.
 
  ABSTRACT  
 
The structures of the liver X receptor LXRbeta (NR1H2) have been determined in complexes with two synthetic ligands, T0901317 and GW3965, to 2.1 and 2.4 A, respectively. Together with its isoform LXRalpha (NR1H3) it regulates target genes involved in metabolism and transport of cholesterol and fatty acids. The two LXRbeta structures reveal a flexible ligand-binding pocket that can adjust to accommodate fundamentally different ligands. The ligand-binding pocket is hydrophobic but with polar or charged residues at the two ends of the cavity. T0901317 takes advantage of this by binding to His-435 close to H12 while GW3965 orients itself with its charged group in the opposite direction. Both ligands induce a fixed "agonist conformation" of helix H12 (also called the AF-2 domain), resulting in a transcriptionally active receptor.
 
  Selected figure(s)  
 
Figure 1.
FIG. 1. Overall structure of the LXR homodimer. The secondary structures are depicted in ribbon representations, each monomer colored red and green, respectively. The helices are numbered 1-12. The ligand T09013 [GenBank] 17 is shown in space filling representation. 		Figure 5.
FIG. 5. Schematic diagram of the interactions between the protein and the ligand T09013 [GenBank] 17 (A) and GW3965 (B). Labels of residues within 4.2 Å to any of the ligands are shown. Hydrogen bonds are depicted with arrows. Residues in boxes have the same conformation with the same ligand in all the three (GW3965) or four (T09013 [GenBank] 17) liganded subunits. Ovals represent residues that show significant differences in their position despite binding to the same ligand. Filled boxes or ovals are residues that change their positions depending on what ligand is binding in the ligand-binding pocket; unfilled boxes or ovals mark residues that are unaffected irrespective of which ligand is bound.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2003, 278, 38821-38828) copyright 2003.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20655343 I.G.Schulman (2010).
Nuclear receptors as drug targets for metabolic disease.
  Adv Drug Deliv Rev, 62, 1307-1315.  
18275080 A.Beautrait, A.S.Karaboga, M.Souchet, and B.Maigret (2008).
Induced fit in liver X receptor beta: a molecular dynamics-based investigation.
  Proteins, 72, 873-882.  
18172702 A.Beautrait, V.Leroux, M.Chavent, L.Ghemtio, M.D.Devignes, M.Smaïl-Tabbone, W.Cai, X.Shao, G.Moreau, P.Bladon, J.Yao, and B.Maigret (2008).
Multiple-step virtual screening using VSM-G: overview and validation of fast geometrical matching enrichment.
  J Mol Model, 14, 135-148.  
18395439 E.J.Reschly, N.Ai, W.J.Welsh, S.Ekins, L.R.Hagey, and M.D.Krasowski (2008).
Ligand specificity and evolution of liver X receptors.
  J Steroid Biochem Mol Biol, 110, 83-94.  
18701720 J.P.Colletier, D.Bourgeois, B.Sanson, D.Fournier, J.L.Sussman, I.Silman, and M.Weik (2008).
Shoot-and-Trap: use of specific x-ray damage to study structural protein dynamics by temperature-controlled cryo-crystallography.
  Proc Natl Acad Sci U S A, 105, 11742-11747.
PDB codes: 2vja 2vjb 2vjc 2vjd 2vt6 2vt7
  19696872 K.M.Honório, L.B.Salum, R.C.Garratt, I.Polikarpov, and A.D.Andricopulo (2008).
Two- and three-dimensional quantitative structure-activity relationships studies on a series of liver x receptor ligands.
  Open Med Chem J, 2, 87-96.  
18160712 K.Suino-Powell, Y.Xu, C.Zhang, Y.G.Tao, W.D.Tolbert, S.S.Simons, and H.E.Xu (2008).
Doubling the size of the glucocorticoid receptor ligand binding pocket by deacylcortivazol.
  Mol Cell Biol, 28, 1915-1923.
PDB code: 3bqd
18651760 M.D.Krasowski, E.J.Reschly, and S.Ekins (2008).
Intrinsic disorder in nuclear hormone receptors.
  J Proteome Res, 7, 4359-4372.  
18221307 N.Malini, H.Rajesh, P.Berwal, S.Phukan, and V.N.Balaji (2008).
Analysis of crystal structures of LXRbeta in relation to plasticity of the ligand-binding domain upon ligand binding.
  Chem Biol Drug Des, 71, 140-154.  
18391212 S.M.Soisson, G.Parthasarathy, A.D.Adams, S.Sahoo, A.Sitlani, C.Sparrow, J.Cui, and J.W.Becker (2008).
Identification of a potent synthetic FXR agonist with an unexpected mode of binding and activation.
  Proc Natl Acad Sci U S A, 105, 5337-5342.
PDB code: 3bej
18389516 Y.Hashimoto (2008).
Thalidomide as a multi-template for development of biologically active compounds.
  Arch Pharm (Weinheim), 341, 536-547.  
17215127 Y.Xue, E.Chao, W.J.Zuercher, T.M.Willson, J.L.Collins, and M.R.Redinbo (2007).
Crystal structure of the PXR-T1317 complex provides a scaffold to examine the potential for receptor antagonism.
  Bioorg Med Chem, 15, 2156-2166.
PDB code: 2o9i
16892386 J.T.Moore, J.L.Collins, and K.H.Pearce (2006).
The nuclear receptor superfamily and drug discovery.
  ChemMedChem, 1, 504-523.  
16823031 Y.Hamuro, S.J.Coales, J.A.Morrow, K.S.Molnar, S.J.Tuske, M.R.Southern, and P.R.Griffin (2006).
Hydrogen/deuterium-exchange (H/D-Ex) of PPARgamma LBD in the presence of various modulators.
  Protein Sci, 15, 1883-1892.  
14996618 H.Gong, and W.Xie (2004).
Orphan nuclear receptors, PXR and LXR: new ligands and therapeutic potential.
  Expert Opin Ther Targets, 8, 49-54.  
15520817 H.Gronemeyer, J.A.Gustafsson, and V.Laudet (2004).
Principles for modulation of the nuclear receptor superfamily.
  Nat Rev Drug Discov, 3, 950-964.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.

 

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