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PDBsum entry 1xnn

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protein ligands links
Hormone/growth factor PDB id
1xnn
Jmol
Contents
Protein chain
247 a.a. *
Ligands
HYQ
Waters ×35
* Residue conservation analysis
PDB id:
1xnn
Name: Hormone/growth factor
Title: Crystal structure of the rat androgen receptor ligand binding domain t877a mutant complex with (3a-alpha-,4- alpha 7-alpha-,7a-alpha-)-3a,4,7,7a-tetrahydro-2-(4-nitro- 1-naphthalenyl)-4,7-ethano-1h-isoindole-1,3(2h)-dione.
Structure: Androgen receptor. Chain: a. Fragment: ligand-binding domain. Synonym: dihydrotestosterone receptor. Engineered: yes. Mutation: yes
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Gene: ar, nr3c4. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Resolution:
2.20Å     R-factor:   0.249     R-free:   0.301
Authors: J.Sack
Key ref: M.E.Salvati et al. (2005). Structure based approach to the design of bicyclic-1H-isoindole-1,3(2H)-dione based androgen receptor antagonists. Bioorg Med Chem Lett, 15, 271-276. PubMed id: 15603938 DOI: 10.1016/j.bmcl.2004.10.085
Date:
05-Oct-04     Release date:   11-Oct-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P15207  (ANDR_RAT) -  Androgen receptor
Seq:
Struc:
 
Seq:
Struc:
902 a.a.
247 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: 10.1016/j.bmcl.2004.10.085 Bioorg Med Chem Lett 15:271-276 (2005)
PubMed id: 15603938  
 
 
Structure based approach to the design of bicyclic-1H-isoindole-1,3(2H)-dione based androgen receptor antagonists.
M.E.Salvati, A.Balog, W.Shan, D.D.Wei, D.Pickering, R.M.Attar, J.Geng, C.A.Rizzo, M.M.Gottardis, R.Weinmann, S.R.Krystek, J.Sack, Y.An, K.Kish.
 
  ABSTRACT  
 
A novel series of isoindoledione based compounds were identified as potent antagonists of the androgen receptor (AR). Co-crystallization of members of this family of inhibitors was successfully accomplished with the T877A AR LBD. A working model of how this class of compounds functions to antagonize the AR was created. Based on this model, it was proposed that expanding the bicyclic portion of the molecule should result in analogs which function as effective antagonists against a variety of AR isoforms. In contrast to what was predicted by the model, SAR around this new series was dictated by the aniline portion rather than the bicyclic portion of the molecule.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20853390 B.Liu, L.Su, J.Geng, J.Liu, and G.Zhao (2010).
Developments in nonsteroidal antiandrogens targeting the androgen receptor.
  ChemMedChem, 5, 1651-1661.  
20708648 W.Gao (2010).
Androgen receptor as a therapeutic target.
  Adv Drug Deliv Rev, 62, 1277-1284.  
  19946220 N.V.Narizhneva, N.D.Tararova, P.Ryabokon, I.Shyshynova, A.Prokvolit, P.G.Komarov, A.A.Purmal, A.V.Gudkov, and K.V.Gurova (2009).
Small molecule screening reveals a transcription-independent pro-survival function of androgen receptor in castration-resistant prostate cancer.
  Cell Cycle, 8, 4155-4167.  
  19079612 R.Narayanan, M.L.Mohler, C.E.Bohl, D.D.Miller, and J.T.Dalton (2008).
Selective androgen receptor modulators in preclinical and clinical development.
  Nucl Recept Signal, 6, e010.  
17300979 V.Nahoum, and W.Bourguet (2007).
Androgen and estrogen receptors: potential of crystallography in the fight against cancer.
  Int J Biochem Cell Biol, 39, 1280-1287.  
17024292 S.M.Ogbomo, and D.J.Burnell (2006).
cis-3,5-Cyclohexadiene-1,2-diol derivatives: facial selectivity in their Diels-Alder reactions with ethylenic, acetylenic and azo dienophiles.
  Org Biomol Chem, 4, 3838-3848.  
16841196 W.Gao, J.Kim, and J.T.Dalton (2006).
Pharmacokinetics and pharmacodynamics of nonsteroidal androgen receptor ligands.
  Pharm Res, 23, 1641-1658.  
16159155 W.Gao, C.E.Bohl, and J.T.Dalton (2005).
Chemistry and structural biology of androgen receptor.
  Chem Rev, 105, 3352-3370.  
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.