3IMY

Structure of TR-beta bound to selective thyromimetic GC-1


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.55 Å
  • R-Value Free: 0.271 
  • R-Value Work: 0.225 
  • R-Value Observed: 0.227 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Structural basis of GC-1 selectivity for thyroid hormone receptor isoforms.

Bleicher, L.Aparicio, R.Nunes, F.M.Martinez, L.Gomes Dias, S.M.Figueira, A.C.M.Santos, M.A.M.Venturelli, W.H.da Silva, R.Donate, P.M.Neves, F.A.Simeoni, L.A.Baxter, J.D.Webb, P.Skaf, M.S.Polikarpov, I.

(2008) BMC Struct Biol 8: 1-13

  • DOI: https://doi.org/10.1186/1472-6807-8-8
  • Primary Citation of Related Structures:  
    3HZF, 3ILZ, 3IMY

  • PubMed Abstract: 

    Thyroid receptors, TRalpha and TRbeta, are involved in important physiological functions such as metabolism, cholesterol level and heart activities. Whereas metabolism increase and cholesterol level lowering could be achieved by TRbeta isoform activation, TRalpha activation affects heart rates. Therefore, beta-selective thyromimetics have been developed as promising drug-candidates for treatment of obesity and elevated cholesterol level. GC-1 [3,5-dimethyl-4-(4'-hydroxy-3'-isopropylbenzyl)-phenoxy acetic acid] has ability to lower LDL cholesterol with 600- to 1400-fold more potency and approximately two- to threefold more efficacy than atorvastatin (Lipitor(c)) in studies in rats, mice and monkeys.


  • Organizational Affiliation

    Instituto de Física de São Carlos, Universidade de São Paulo, Avenida Trabalhador São Carlense, 400 CEP 13560-970 São Carlos, SP, Brazil. lbleicher@if.sc.usp.br


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Thyroid hormone receptor beta261Homo sapiensMutation(s): 0 
Gene Names: ERBA2NR1A2THR1THRB
UniProt & NIH Common Fund Data Resources
Find proteins for P10828 (Homo sapiens)
Explore P10828 
Go to UniProtKB:  P10828
PHAROS:  P10828
GTEx:  ENSG00000151090 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP10828
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
B72
Query on B72

Download Ideal Coordinates CCD File 
B [auth A]{4-[4-hydroxy-3-(1-methylethyl)benzyl]-3,5-dimethylphenoxy}acetic acid
C20 H24 O4
QNAZTOHXCZPOSA-UHFFFAOYSA-N
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
CAS
Query on CAS
A
L-PEPTIDE LINKINGC5 H12 As N O2 SCYS
Binding Affinity Annotations 
IDSourceBinding Affinity
B72 BindingDB:  3IMY Ki: 0.32 (nM) from 1 assay(s)
Kd: min: 0.07, max: 0.2 (nM) from 3 assay(s)
EC50: min: 2.82, max: 18 (nM) from 3 assay(s)
PDBBind:  3IMY Kd: 0.2 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.55 Å
  • R-Value Free: 0.271 
  • R-Value Work: 0.225 
  • R-Value Observed: 0.227 
  • Space Group: P 31 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 68.996α = 90
b = 68.996β = 90
c = 130.861γ = 120
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
PHENIXrefinement
PDB_EXTRACTdata extraction
MAR345dtbdata collection
AMoREphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2009-09-08
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2017-11-01
    Changes: Refinement description
  • Version 1.3: 2023-09-06
    Changes: Data collection, Database references, Derived calculations, Refinement description