PDBsum entry 2qr9

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protein ligands Protein-protein interface(s) links
Transcription PDB id
Protein chains
242 a.a. *
11 a.a. *
HZ3 ×2
Waters ×159
* Residue conservation analysis
PDB id:
Name: Transcription
Title: Crystal structure of the estrogen receptor alpha ligand bind complexed with an oxabicyclic derivative compound
Structure: Estrogen receptor. Chain: a, b. Fragment: steroid-binding region, residues 298-554. Synonym: er, estradiol receptor, er-alpha. Engineered: yes. Mutation: yes. Nuclear receptor coactivator 2. Chain: c, d. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: esr1, esr, nr3a1. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: the peptide is naturally found in mus muscul (mouse).
2.00Å     R-factor:   0.216     R-free:   0.262
Authors: K.W.Nettles,J.B.Bruning
Key ref:
K.W.Nettles et al. (2008). NFkappaB selectivity of estrogen receptor ligands revealed by comparative crystallographic analyses. Nat Chem Biol, 4, 241-247. PubMed id: 18344977 DOI: 10.1038/nchembio.76
27-Jul-07     Release date:   18-Mar-08    
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Protein chains
Pfam   ArchSchema ?
P03372  (ESR1_HUMAN) -  Estrogen receptor
595 a.a.
242 a.a.*
Protein chain
Pfam   ArchSchema ?
Q61026  (NCOA2_MOUSE) -  Nuclear receptor coactivator 2
1462 a.a.
11 a.a.
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 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     3 terms  


DOI no: 10.1038/nchembio.76 Nat Chem Biol 4:241-247 (2008)
PubMed id: 18344977  
NFkappaB selectivity of estrogen receptor ligands revealed by comparative crystallographic analyses.
K.W.Nettles, J.B.Bruning, G.Gil, J.Nowak, S.K.Sharma, J.B.Hahm, K.Kulp, R.B.Hochberg, H.Zhou, J.A.Katzenellenbogen, B.S.Katzenellenbogen, Y.Kim, A.Joachmiak, G.L.Greene.
Our understanding of how steroid hormones regulate physiological functions has been significantly advanced by structural biology approaches. However, progress has been hampered by misfolding of the ligand binding domains in heterologous expression systems and by conformational flexibility that interferes with crystallization. Here, we show that protein folding problems that are common to steroid hormone receptors are circumvented by mutations that stabilize well-characterized conformations of the receptor. We use this approach to present the structure of an apo steroid receptor that reveals a ligand-accessible channel allowing soaking of preformed crystals. Furthermore, crystallization of different pharmacological classes of compounds allowed us to define the structural basis of NFkappaB-selective signaling through the estrogen receptor, thus revealing a unique conformation of the receptor that allows selective suppression of inflammatory gene expression. The ability to crystallize many receptor-ligand complexes with distinct pharmacophores allows one to define structural features of signaling specificity that would not be apparent in a single structure.
  Selected figure(s)  
Figure 2.
(a) Shown is the structure of tamoxifen-bound ER (PDB code 3ERT) as a ribbon diagram. Helices 3–5 are colored pink, and helix 12 is colored red. (b) Molecular modeling suggests that the mutation L536S of ER promotes a stabilizing interaction between helix 12 and Glu380 in helix 3.
Figure 3.
(a) The structure of genistein-bound ER Y537S is depicted as a ribbon diagram, showing only a portion of the molecule that interacts with the ligand. The closed interface between helix 11 and L7-8 is shown by a red circle.
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Chem Biol (2008, 4, 241-247) copyright 2008.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20063036 A.le Maire, W.Bourguet, and P.Balaguer (2010).
A structural view of nuclear hormone receptor: endocrine disruptor interactions.
  Cell Mol Life Sci, 67, 1219-1237.
PDB code: 3kwy
20924370 J.B.Bruning, A.A.Parent, G.Gil, M.Zhao, J.Nowak, M.C.Pace, C.L.Smith, P.V.Afonine, P.D.Adams, J.A.Katzenellenbogen, and K.W.Nettles (2010).
Coupling of receptor conformation and ligand orientation determine graded activity.
  Nat Chem Biol, 6, 837-843.
PDB codes: 2qxs 2qzo 3os8 3os9 3osa
20230029 S.H.Kim, J.R.Gunther, and J.A.Katzenellenbogen (2010).
Monitoring a coordinated exchange process in a four-component biological interaction system: development of a time-resolved terbium-based one-donor/three-acceptor multicolor FRET system.
  J Am Chem Soc, 132, 4685-4692.  
20922740 S.Möcklinghoff, R.Rose, M.Carraz, A.Visser, C.Ottmann, and L.Brunsveld (2010).
Synthesis and crystal structure of a phosphorylated estrogen receptor ligand binding domain.
  Chembiochem, 11, 2251-2254.
PDB codes: 3oll 3ols
20404154 S.N.Giraud, C.M.Caron, D.Pham-Dinh, P.Kitabgi, and A.B.Nicot (2010).
Estradiol inhibits ongoing autoimmune neuroinflammation and NFkappaB-dependent CCL2 expression in reactive astrocytes.
  Proc Natl Acad Sci U S A, 107, 8416-8421.  
19372222 H.C.Raaijmakers, J.E.Versteegh, and J.C.Uitdehaag (2009).
The X-ray Structure of RU486 Bound to the Progesterone Receptor in a Destabilized Agonistic Conformation.
  J Biol Chem, 284, 19572-19579.
PDB code: 2w8y
  20087432 I.J.McEwan, and A.M.Nardulli (2009).
Nuclear hormone receptor architecture - form and dynamics: The 2009 FASEB Summer Conference on Dynamic Structure of the Nuclear Hormone Receptors.
  Nucl Recept Signal, 7, e011.  
18841988 S.H.Kim, J.R.Gunther, and J.A.Katzenellenbogen (2008).
Nonclassical SNAPFL analogue as a Cy5 resonance energy transfer partner.
  Org Lett, 10, 4931-4934.  
18347588 S.Mader (2008).
Fast-tracking steroid receptor crystallization.
  Nat Chem Biol, 4, 226-227.  
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 code is shown on the right.