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PDBsum entry 3l3z

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protein ligands Protein-protein interface(s) links
Protein binding PDB id
3l3z
Jmol PyMol
Contents
Protein chains
249 a.a. *
12 a.a. *
Ligands
DHT
Waters ×141
* Residue conservation analysis
PDB id:
3l3z
Name: Protein binding
Title: Crystal structure of dht-bound androgen receptor in complex with the third motif of steroid receptor coactivator 3
Structure: Androgen receptor. Chain: a. Fragment: ligand binding domain. Synonym: dihydrotestosterone receptor, nuclear receptor subfamily 3 group c member 4. Engineered: yes. Nuclear receptor coactivator 3. Chain: b. Fragment: receptor binding motif 3.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: ar, dhtr, nr3c4. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Organism_taxid: 9606
Resolution:
2.00Å     R-factor:   0.196     R-free:   0.243
Authors: X.E.Zhou,K.M.Suino-Powell,J.Li,A.He,J.P.Mackeigan,K.Melcher, E.-L.Yong,H.E.Xu
Key ref: X.E.Zhou et al. (2010). Identification of SRC3/AIB1 as a preferred coactivator for hormone-activated androgen receptor. J Biol Chem, 285, 9161-9171. PubMed id: 20086010
Date:
18-Dec-09     Release date:   12-Jan-10    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P10275  (ANDR_HUMAN) -  Androgen receptor
Seq:
Struc:
 
Seq:
Struc:
919 a.a.
249 a.a.*
Protein chain
Pfam   ArchSchema ?
Q9Y6Q9  (NCOA3_HUMAN) -  Nuclear receptor coactivator 3
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
1424 a.a.
12 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: Chain B: E.C.2.3.1.48  - Histone acetyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Acetyl-CoA + [histone] = CoA + acetyl-[histone]
Acetyl-CoA
+ [histone]
= CoA
+ acetyl-[histone]
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 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     2 terms  

 

 
    Added reference    
 
 
J Biol Chem 285:9161-9171 (2010)
PubMed id: 20086010  
 
 
Identification of SRC3/AIB1 as a preferred coactivator for hormone-activated androgen receptor.
X.E.Zhou, K.M.Suino-Powell, J.Li, Y.He, J.P.Mackeigan, K.Melcher, E.L.Yong, H.E.Xu.
 
  ABSTRACT  
 
Transcription activation by androgen receptor (AR), which depends on recruitment of coactivators, is required for the initiation and progression of prostate cancer, yet the mechanisms of how hormone-activated AR interacts with coactivators remain unclear. This is because AR, unlike any other nuclear receptor, prefers its own N-terminal FXXLF motif to the canonical LXXLL motifs of coactivators. Through biochemical and crystallographic studies, we identify that steroid receptor coactivator-3 (SRC3) (also named as amplified in breast cancer-1 or AIB1) interacts strongly with AR via synergistic binding of its first and third LXXLL motifs. Mutagenesis and functional studies confirm that SRC3 is a preferred coactivator for hormone-activated AR. Importantly, AR mutations found in prostate cancer patients correlate with their binding potency to SRC3, corroborating with the emerging role of SRC3 as a prostate cancer oncogene. These results provide a molecular mechanism for the selective utilization of SRC3 by hormone-activated AR, and they link the functional relationship between AR and SRC3 to the development and growth of prostate cancer.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21826082 T.A.Yap, A.Zivi, A.Omlin, and J.S.de Bono (2011).
The changing therapeutic landscape of castration-resistant prostate cancer.
  Nat Rev Clin Oncol, 8, 597-610.  
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.

 

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