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PDBsum entry 1n46

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protein ligands Protein-protein interface(s) links
Transcription PDB id
1n46
Jmol
Contents
Protein chain
248 a.a. *
Ligands
PFA ×2
Waters ×114
* Residue conservation analysis
PDB id:
1n46
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)
Resolution:
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
Date:
30-Oct-02     Release date:   22-Apr-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P10828  (THB_HUMAN) -  Thyroid hormone receptor beta
Seq:
Struc:
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.
 
  ABSTRACT  
 
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.  
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.