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PDBsum entry 1gs4

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protein ligands links
Androgen receptor PDB id
1gs4
Jmol
Contents
Protein chain
244 a.a. *
Ligands
ZK5
PO4
Waters ×106
* Residue conservation analysis
PDB id:
1gs4
Name: Androgen receptor
Title: Structural basis for the glucocorticoid response in a mutant human androgen receptor (arccr) derived from an androgen-independent prostate cancer
Structure: Androgen receptor. Chain: a. Fragment: ligand-binding domain, residues 670-917. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 511693. Expression_system_cell_line: de3
Resolution:
1.95Å     R-factor:   0.205     R-free:   0.285
Authors: P.M.Matias,M.A.Carrondo,R.Coelho,M.Thomaz,X.-Y.Zhao,A.Wegg, K.Crusius,U.Egner,P.Donner
Key ref: P.M.Matias et al. (2002). Structural basis for the glucocorticoid response in a mutant human androgen receptor (AR(ccr)) derived from an androgen-independent prostate cancer. J Med Chem, 45, 1439-1446. PubMed id: 11906285 DOI: 10.1021/jm011072j
Date:
27-Dec-01     Release date:   16-Jan-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P10275  (ANDR_HUMAN) -  Androgen receptor
Seq:
Struc:
 
Seq:
Struc:
919 a.a.
244 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 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: 10.1021/jm011072j J Med Chem 45:1439-1446 (2002)
PubMed id: 11906285  
 
 
Structural basis for the glucocorticoid response in a mutant human androgen receptor (AR(ccr)) derived from an androgen-independent prostate cancer.
P.M.Matias, M.A.Carrondo, R.Coelho, M.Thomaz, X.Y.Zhao, A.Wegg, K.Crusius, U.Egner, P.Donner.
 
  ABSTRACT  
 
The crystal structure of a mutant androgen receptor (AR) ligand-binding domain (LBD) in complex with the agonist 9alpha-fluorocortisol has been determined at 1.95 A resolution. This mutant AR contains two mutations (L701H and T877A) and was previously reported as a high-affinity cortisol/cortisone responsive AR (AR(ccr)) isolated from the androgen-independent human prostate cancer cell lines MDA PCa 2a and 2b (Zhao et al. Nature Med. 2000, 6, 703-6). The three-dimensional structure of the AR(ccr) LBD complexed with 9alpha-fluorocortisol shows the typical conformation of an agonist-bound nuclear receptor in which helix 12 is precisely positioned as a "lid" for the ligand-binding pocket. Binding of 9alpha-fluorocortisol to the AR(ccr) involves favorable hydrogen bond patterns on the C17 and C21 substituents of the ligand due to the mutations at 701 and 877 in the AR(ccr). Our studies provide the first structural explanation for the glucocorticoid activation of AR(ccr), which is important for the development of new therapeutic treatments for androgen-independent prostate cancer.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21251949 T.B.Knudsen, K.A.Houck, N.S.Sipes, A.V.Singh, R.S.Judson, M.T.Martin, A.Weissman, N.C.Kleinstreuer, H.M.Mortensen, D.M.Reif, J.R.Rabinowitz, R.W.Setzer, A.M.Richard, D.J.Dix, and R.J.Kavlock (2011).
Activity profiles of 309 ToxCastâ„¢ chemicals evaluated across 292 biochemical targets.
  Toxicology, 282, 1.  
18800375 J.P.Bergerat, and J.Céraline (2009).
Pleiotropic functional properties of androgen receptor mutants in prostate cancer.
  Hum Mutat, 30, 145-157.  
18986533 Y.K.Lau, M.K.Chadha, A.Litwin, and D.L.Trump (2008).
A dramatic, objective antiandrogen withdrawal response: case report and review of the literature.
  J Hematol Oncol, 1, 21.  
17591767 E.B.Askew, R.T.Gampe, T.B.Stanley, J.L.Faggart, and E.M.Wilson (2007).
Modulation of androgen receptor activation function 2 by testosterone and dihydrotestosterone.
  J Biol Chem, 282, 25801-25816.
PDB codes: 2q7i 2q7j 2q7k 2q7l
17336451 K.Robzyk, H.Oen, G.Buchanan, L.M.Butler, W.D.Tilley, A.K.Mandal, N.Rosen, and A.J.Caplan (2007).
Uncoupling of hormone-dependence from chaperone-dependence in the L701H mutation of the androgen receptor.
  Mol Cell Endocrinol, 268, 67-74.  
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.  
17606915 W.H.Bisson, A.V.Cheltsov, N.Bruey-Sedano, B.Lin, J.Chen, N.Goldberger, L.T.May, A.Christopoulos, J.T.Dalton, P.M.Sexton, X.K.Zhang, and R.Abagyan (2007).
Discovery of antiandrogen activity of nonsteroidal scaffolds of marketed drugs.
  Proc Natl Acad Sci U S A, 104, 11927-11932.  
16365032 B.He, R.T.Gampe, A.T.Hnat, J.L.Faggart, J.T.Minges, F.S.French, and E.M.Wilson (2006).
Probing the functional link between androgen receptor coactivator and ligand-binding sites in prostate cancer and androgen insensitivity.
  J Biol Chem, 281, 6648-6663.  
16828557 D.J.Hwang, J.Yang, H.Xu, I.M.Rakov, M.L.Mohler, J.T.Dalton, and D.D.Miller (2006).
Arylisothiocyanato selective androgen receptor modulators (SARMs) for prostate cancer.
  Bioorg Med Chem, 14, 6525-6538.  
16641486 K.Pereira de Jésus-Tran, P.L.Côté, L.Cantin, J.Blanchet, F.Labrie, and R.Breton (2006).
Comparison of crystal structures of human androgen receptor ligand-binding domain complexed with various agonists reveals molecular determinants responsible for binding affinity.
  Protein Sci, 15, 987-999.
PDB codes: 2am9 2ama 2amb
16129672 C.E.Bohl, D.D.Miller, J.Chen, C.E.Bell, and J.T.Dalton (2005).
Structural basis for accommodation of nonsteroidal ligands in the androgen receptor.
  J Biol Chem, 280, 37747-37754.
PDB codes: 2ax6 2ax7 2ax8 2ax9 2axa
15833816 C.E.Bohl, W.Gao, D.D.Miller, C.E.Bell, and J.T.Dalton (2005).
Structural basis for antagonism and resistance of bicalutamide in prostate cancer.
  Proc Natl Acad Sci U S A, 102, 6201-6206.
PDB code: 1z95
15994236 F.Schaufele, X.Carbonell, M.Guerbadot, S.Borngraeber, M.S.Chapman, A.A.Ma, J.N.Miner, and M.I.Diamond (2005).
The structural basis of androgen receptor activation: intramolecular and intermolecular amino-carboxy interactions.
  Proc Natl Acad Sci U S A, 102, 9802-9807.  
16159155 W.Gao, C.E.Bohl, and J.T.Dalton (2005).
Chemistry and structural biology of androgen receptor.
  Chem Rev, 105, 3352-3370.  
15264248 G.Buchanan, P.S.Craft, M.Yang, A.Cheong, J.Prescott, L.Jia, G.A.Coetzee, and W.D.Tilley (2004).
PC-3 cells with enhanced androgen receptor signaling: a model for clonal selection in prostate cancer.
  Prostate, 60, 352-366.  
12441355 G.Liao, L.Y.Chen, A.Zhang, A.Godavarthy, F.Xia, J.C.Ghosh, H.Li, and J.D.Chen (2003).
Regulation of androgen receptor activity by the nuclear receptor corepressor SMRT.
  J Biol Chem, 278, 5052-5061.  
  12676613 H.Tamura, H.Yoshikawa, K.W.Gaido, S.M.Ross, R.K.DeLisle, W.J.Welsh, and A.M.Richard (2003).
Interaction of organophosphate pesticides and related compounds with the androgen receptor.
  Environ Health Perspect, 111, 545-552.  
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.