PDBsum entry 1n46

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Transcription PDB id
Protein chain
248 a.a. *
PFA ×2
Waters ×114
* Residue conservation analysis
PDB id:
Name: Transcription
Title: Crystal structure of human tr beta ligand-binding domain complexed with a potent subtype-selective thyromimetic
Structure: Thyroid hormone receptor beta-1. Chain: a, b. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Dimer (from PQS)
2.20Å     R-factor:   0.195     R-free:   0.256
Authors: R.L.Dow,S.R.Schneider,E.S.Paight,R.F.Hank,P.Chiang, P.Cornelius,E.Lee,W.P.Newsome,A.G.Swick,J.Spitzer, D.M.Hargrove,T.A.Patterson,J.Pandit,B.A.Chrunyk,P.K.Lemotte D.E.Danley,M.H.Rosner,M.J.Ammirati,S.P.Simons,G.K.Schulte, B.F.Tate,P.Dasilva-Jardine
Key ref: R.L.Dow et al. (2003). Discovery of a novel series of 6-azauracil-based thyroid hormone receptor ligands: potent, TR beta subtype-selective thyromimetics. Bioorg Med Chem Lett, 13, 379-382. PubMed id: 12565933 DOI: 10.1016/S0960-894X(02)00947-2
30-Oct-02     Release date:   22-Apr-03    
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Protein chains
Pfam   ArchSchema ?
P10828  (THB_HUMAN) -  Thyroid hormone receptor beta
461 a.a.
248 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     nucleus   1 term 
  Biological process     steroid hormone mediated signaling pathway   2 terms 
  Biochemical function     DNA binding     4 terms  


DOI no: 10.1016/S0960-894X(02)00947-2 Bioorg Med Chem Lett 13:379-382 (2003)
PubMed id: 12565933  
Discovery of a novel series of 6-azauracil-based thyroid hormone receptor ligands: potent, TR beta subtype-selective thyromimetics.
R.L.Dow, S.R.Schneider, E.S.Paight, R.F.Hank, P.Chiang, P.Cornelius, E.Lee, W.P.Newsome, A.G.Swick, J.Spitzer, D.M.Hargrove, T.A.Patterson, J.Pandit, B.A.Chrunyk, P.K.LeMotte, D.E.Danley, M.H.Rosner, M.J.Ammirati, S.P.Simons, G.K.Schulte, B.F.Tate, P.DaSilva-Jardine.
In this communication, we wish to describe the discovery of a novel series of 6-azauracil-based thyromimetics that possess up to 100-fold selectivities for binding and functional activation of the beta(1)-isoform of the thyroid receptor family. Structure-activity relationship studies on the 3,5- and 3'-positions provided compounds with enhanced TR beta affinity and selectivity. Key binding interactions between the 6-azauracil moiety and the receptor have been determined through of X-ray crystallographic analysis.

Literature references that cite this PDB file's key reference

  PubMed id Reference
19582836 G.Wohlfahrt, J.Sipilä, and L.O.Pietilä (2009).
Field-based comparison of ligand and coactivator binding sites of nuclear receptors.
  Biopolymers, 91, 884-894.  
18237438 L.Bleicher, R.Aparicio, F.M.Nunes, L.Martinez, S.M.Gomes Dias, A.C.Figueira, M.A.Santos, W.H.Venturelli, R.da Silva, P.M.Donate, F.A.Neves, L.A.Simeoni, J.D.Baxter, P.Webb, M.S.Skaf, and I.Polikarpov (2008).
Structural basis of GC-1 selectivity for thyroid hormone receptor isoforms.
  BMC Struct Biol, 8, 8.
PDB codes: 3hzf 3ilz 3imy
17096449 A.Vedani, M.Zumstein, M.A.Lill, and B.Ernst (2007).
Simulating alpha/beta Selectivity at the Human Thyroid Hormone Receptor: Consensus Scoring Using Multidimensional QSAR.
  ChemMedChem, 2, 78-87.  
17524652 H.Liu, and P.Gramatica (2007).
QSAR study of selective ligands for the thyroid hormone receptor beta.
  Bioorg Med Chem, 15, 5251-5261.  
15388935 F.M.Nunes, R.Aparicio, M.A.Santos, R.V.Portugal, S.M.Dias, F.A.Neves, L.A.Simeoni, J.D.Baxter, P.Webb, and I.Polikarpov (2004).
Crystallization and preliminary X-ray diffraction studies of isoform alpha1 of the human thyroid hormone receptor ligand-binding domain.
  Acta Crystallogr D Biol Crystallogr, 60, 1867-1870.  
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