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PDBsum entry 1i37
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Hormone/growth factor PDB id
1i37

 

 

 

 

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JSmol PyMol  
Contents
Protein chain
246 a.a. *
Ligands
DHT
Waters ×106
* Residue conservation analysis
PDB id:
1i37
Name: Hormone/growth factor
Title: Crystal structure of the rat androgen receptor ligand binding domain complex with dihydrotestosterone
Structure: Androgen receptor. Chain: a. Fragment: ligand-binding domain. Synonym: dihydrotestosterone receptor. Engineered: yes
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Resolution:
2.00Å     R-factor:   0.242     R-free:   0.312
Authors: J.S.Sack
Key ref:
J.S.Sack et al. (2001). Crystallographic structures of the ligand-binding domains of the androgen receptor and its T877A mutant complexed with the natural agonist dihydrotestosterone. Proc Natl Acad Sci U S A, 98, 4904-4909. PubMed id: 11320241 DOI: 10.1073/pnas.081565498
Date:
13-Feb-01     Release date:   21-Mar-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P15207  (ANDR_RAT) -  Androgen receptor from Rattus norvegicus
Seq:
Struc: 		 
Seq:
Struc: 		902 a.a.
246 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 

 
DOI no: 10.1073/pnas.081565498 Proc Natl Acad Sci U S A 98:4904-4909 (2001)
PubMed id: 11320241  
 
 
Crystallographic structures of the ligand-binding domains of the androgen receptor and its T877A mutant complexed with the natural agonist dihydrotestosterone.
J.S.Sack, K.F.Kish, C.Wang, R.M.Attar, S.E.Kiefer, Y.An, G.Y.Wu, J.E.Scheffler, M.E.Salvati, S.R.Krystek, R.Weinmann, H.M.Einspahr.
 
  ABSTRACT  
 
The structures of the ligand-binding domains (LBD) of the wild-type androgen receptor (AR) and the T877A mutant corresponding to that in LNCaP cells, both bound to dihydrotestosterone, have been refined at 2.0 A resolution. In contrast to the homodimer seen in the retinoid-X receptor and estrogen receptor LBD structures, the AR LBD is monomeric, possibly because of the extended C terminus of AR, which lies in a groove at the dimerization interface. Binding of the natural ligand dihydrotestosterone by the mutant LBD involves interactions with the same residues as in the wild-type receptor, with the exception of the side chain of threonine 877, which is an alanine residue in the mutant. This structural difference in the binding pocket can explain the ability of the mutant AR found in LNCaP cells (T877A) to accommodate progesterone and other ligands that the wild-type receptor cannot.
 
  Selected figure(s)  
 
Figure 1.
Fig. 1. Chemical structures of DHT and progesterone. 		Figure 4.
Fig. 4. Ribbon-style drawing of the AR LBD. The substrate DHT and the side chains that interact with it are shown as ball-and-stick figures. Figs. 5, 6, and 8 were drawn by using ICM Ver. 2.
 
  Figures were selected by an automated process.  

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 ToxCast™ chemicals evaluated across 292 biochemical targets.
  Toxicology, 282, 1.  
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.  
20007693 D.J.van de Wijngaart, M.Molier, S.J.Lusher, R.Hersmus, G.Jenster, J.Trapman, and H.J.Dubbink (2010).
Systematic structure-function analysis of androgen receptor Leu701 mutants explains the properties of the prostate cancer mutant L701H.
  J Biol Chem, 285, 5097-5105.  
20723571 L.Jin, and Y.Li (2010).
Structural and functional insights into nuclear receptor signaling.
  Adv Drug Deliv Rev, 62, 1218-1226.  
20148675 P.Huang, V.Chandra, and F.Rastinejad (2010).
Structural overview of the nuclear receptor superfamily: insights into physiology and therapeutics.
  Annu Rev Physiol, 72, 247-272.  
20817759 R.Goyanka, S.Das, H.H.Samuels, and T.Cardozo (2010).
Nuclear receptor engineering based on novel structure activity relationships revealed by farnesyl pyrophosphate.
  Protein Eng Des Sel, 23, 809-815.  
21318111 R.Hu, S.R.Denmeade, and J.Luo (2010).
Molecular processes leading to aberrant androgen receptor signaling and castration resistance in prostate cancer.
  Expert Rev Endocrinol Metab, 5, 753-764.  
20708648 W.Gao (2010).
Androgen receptor as a therapeutic target.
  Adv Drug Deliv Rev, 62, 1277-1284.  
19362102 C.Byrne, S.D.Divekar, G.B.Storchan, D.A.Parodi, and M.B.Martin (2009).
Cadmium--a metallohormone?
  Toxicol Appl Pharmacol, 238, 266-271.  
19721807 G.N.Brooke, and C.L.Bevan (2009).
The role of androgen receptor mutations in prostate cancer progression.
  Curr Genomics, 10, 18-25.  
19178528 R.Tadokoro, T.Bunch, J.W.Schwabe, I.A.Hughes, and J.C.Murphy (2009).
Comparison of the molecular consequences of different mutations at residue 754 and 690 of the androgen receptor (AR) and androgen insensitivity syndrome (AIS) phenotype.
  Clin Endocrinol (Oxf), 71, 253-260.  
20009327 S.B.Kim, Y.Umezawa, and H.Tao (2009).
Determination of the androgenicity of ligands using a single-chain probe carrying androgen receptor N-terminal peptides.
  Anal Sci, 25, 1415-1420.  
19644954 T.Kimura, H.Kiyota, D.Nakata, T.Masaki, M.Kusaka, and S.Egawa (2009).
A novel androgen-dependent prostate cancer xenograft model derived from skin metastasis of a Japanese patient.
  Prostate, 69, 1660-1667.  
19796750 Y.Chen, N.J.Clegg, and H.I.Scher (2009).
Anti-androgens and androgen-depleting therapies in prostate cancer: new agents for an established target.
  Lancet Oncol, 10, 981-991.  
  18612376 F.Claessens, S.Denayer, N.Van Tilborgh, S.Kerkhofs, C.Helsen, and A.Haelens (2008).
Diverse roles of androgen receptor (AR) domains in AR-mediated signaling.
  Nucl Recept Signal, 6, e008.  
18182971 J.Waxman, and S.Ngan (2008).
Androgen resistance in prostate cancer.
  Br J Cancer, 98, 1.  
18852122 M.C.Hodgson, H.C.Shen, A.N.Hollenberg, and S.P.Balk (2008).
Structural basis for nuclear receptor corepressor recruitment by antagonist-liganded androgen receptor.
  Mol Cancer Ther, 7, 3187-3194.  
  19052375 M.Thauvin, C.Robin-Jagerschmidt, F.Nique, P.Mollat, D.Fleury, and T.Prangé (2008).
Crystallization and preliminary X-ray analysis of the human androgen receptor ligand-binding domain with a coactivator-like peptide and selective androgen receptor modulators.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 1159-1162.  
18095383 M.Thevis, M.Kohler, N.Schlörer, M.Kamber, A.Kühn, M.W.Linscheid, and W.Schänzer (2008).
Mass spectrometry of hydantoin-derived selective androgen receptor modulators.
  J Mass Spectrom, 43, 639-650.  
  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.  
19094205 V.Douard, F.Brunet, B.Boussau, I.Ahrens, V.Vlaeminck-Guillem, B.Haendler, V.Laudet, and Y.Guiguen (2008).
The fate of the duplicated androgen receptor in fishes: a late neofunctionalization event?
  BMC Evol Biol, 8, 336.  
18637017 Y.D.Li, Y.Lu, G.C.Chen, and J.Lu (2008).
An S296R mutation in the human androgen receptor causes activation of the receptor by non-androgenic steroids and stronger inhibition by the nuclear receptor corepressor N-coR.
  Clin Exp Pharmacol Physiol, 35, 1252-1257.  
17164529 A.M.Hassell, G.An, R.K.Bledsoe, J.M.Bynum, H.L.Carter, S.J.Deng, R.T.Gampe, T.E.Grisard, K.P.Madauss, R.T.Nolte, W.J.Rocque, L.Wang, K.L.Weaver, S.P.Williams, G.B.Wisely, R.Xu, and L.M.Shewchuk (2007).
Crystallization of protein-ligand complexes.
  Acta Crystallogr D Biol Crystallogr, 63, 72-79.  
17311914 C.E.Bohl, Z.Wu, D.D.Miller, C.E.Bell, and J.T.Dalton (2007).
Crystal structure of the T877A human androgen receptor ligand-binding domain complexed to cyproterone acetate provides insight for ligand-induced conformational changes and structure-based drug design.
  J Biol Chem, 282, 13648-13655.
PDB code: 2oz7
17306029 M.E.Baker, C.Chandsawangbhuwana, and N.Ollikainen (2007).
Structural analysis of the evolution of steroid specificity in the mineralocorticoid and glucocorticoid receptors.
  BMC Evol Biol, 7, 24.  
17163421 R.Chmelar, G.Buchanan, E.F.Need, W.Tilley, and N.M.Greenberg (2007).
Androgen receptor coregulators and their involvement in the development and progression of prostate cancer.
  Int J Cancer, 120, 719-733.  
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.  
16434567 J.Yang, C.E.Bohl, V.A.Nair, S.M.Mustafa, S.S.Hong, D.D.Miller, and J.T.Dalton (2006).
Preclinical pharmacology of a nonsteroidal ligand for androgen receptor-mediated imaging of prostate cancer.
  J Pharmacol Exp Ther, 317, 402-408.  
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
16759873 P.Marwah, A.Marwah, H.A.Lardy, H.Miyamoto, and C.Chang (2006).
C19-steroids as androgen receptor modulators: design, discovery, and structure-activity relationship of new steroidal androgen receptor antagonists.
  Bioorg Med Chem, 14, 5933-5947.  
16434973 T.S.Mantoni, G.Reid, and M.D.Garrett (2006).
Androgen receptor activity is inhibited in response to genotoxic agents in a p53-independent manner.
  Oncogene, 25, 3139-3149.  
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
15684382 C.S.Yang, M.J.Vitto, S.A.Busby, B.A.Garcia, C.T.Kesler, D.Gioeli, J.Shabanowitz, D.F.Hunt, K.Rundell, D.L.Brautigan, and B.M.Paschal (2005).
Simian virus 40 small t antigen mediates conformation-dependent transfer of protein phosphatase 2A onto the androgen receptor.
  Mol Cell Biol, 25, 1298-1308.  
15860367 C.Y.Chang, and D.P.McDonnell (2005).
Androgen receptor-cofactor interactions as targets for new drug discovery.
  Trends Pharmacol Sci, 26, 225-228.  
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.  
15617028 G.Chen, X.Wang, S.Zhang, Y.Lu, Y.Sun, J.Zhang, Z.Li, and J.Lu (2005).
Androgen receptor mutants detected in recurrent prostate cancer exhibit diverse functional characteristics.
  Prostate, 63, 395-406.  
15657128 G.Han, G.Buchanan, M.Ittmann, J.M.Harris, X.Yu, F.J.Demayo, W.Tilley, and N.M.Greenberg (2005).
Mutation of the androgen receptor causes oncogenic transformation of the prostate.
  Proc Natl Acad Sci U S A, 102, 1151-1156.  
16166218 J.Chen, D.J.Hwang, K.Chung, C.E.Bohl, S.J.Fisher, D.D.Miller, and J.T.Dalton (2005).
In vitro and in vivo structure-activity relationships of novel androgen receptor ligands with multiple substituents in the B-ring.
  Endocrinology, 146, 5444-5454.  
15994457 J.Chen, J.Kim, and J.T.Dalton (2005).
Discovery and therapeutic promise of selective androgen receptor modulators.
  Mol Interv, 5, 173-188.  
15908963 J.Fagart, J.Huyet, G.M.Pinon, M.Rochel, C.Mayer, and M.E.Rafestin-Oblin (2005).
Crystal structure of a mutant mineralocorticoid receptor responsible for hypertension.
  Nat Struct Mol Biol, 12, 554-555.
PDB codes: 1y9r 1ya3
15980170 L.Martínez, M.T.Sonoda, P.Webb, J.D.Baxter, M.S.Skaf, and I.Polikarpov (2005).
Molecular dynamics simulations reveal multiple pathways of ligand dissociation from thyroid hormone receptors.
  Biophys J, 89, 2011-2023.  
16351736 P.D'Ursi, E.Salvi, P.Fossa, L.Milanesi, and E.Rovida (2005).
Modelling the interaction of steroid receptors with endocrine disrupting chemicals.
  BMC Bioinformatics, 6, S10.  
16107211 P.E.Olsson, A.H.Berg, J.von Hofsten, B.Grahn, A.Hellqvist, A.Larsson, J.Karlsson, C.Modig, B.Borg, and P.Thomas (2005).
Molecular cloning and characterization of a nuclear androgen receptor activated by 11-ketotestosterone.
  Reprod Biol Endocrinol, 3, 37.  
15789554 R.Maltais, C.Mercier, F.Labrie, and D.Poirier (2005).
Solid-phase synthesis of model libraries of 3alpha,17beta-dihydroxy-16alpha-(aminoethyl-N-substituted)-5alpha-androstanes for the development of steroidal therapeutic agents.
  Mol Divers, 9, 67-79.  
16159155 W.Gao, C.E.Bohl, and J.T.Dalton (2005).
Chemistry and structural biology of androgen receptor.
  Chem Rev, 105, 3352-3370.  
15983373 X.Ye, S.J.Han, S.Y.Tsai, F.J.DeMayo, J.Xu, M.J.Tsai, and B.W.O'Malley (2005).
Roles of steroid receptor coactivator (SRC)-1 and transcriptional intermediary factor (TIF) 2 in androgen receptor activity in mice.
  Proc Natl Acad Sci U S A, 102, 9487-9492.  
  16971966 Y.S.Zhu (2005).
Molecular Basis of Steroid Action in the Prostate.
  Cellscience, 1, 27-55.  
14716738 C.B.Lazier, L.N.Thomas, R.C.Douglas, J.P.Vessey, and R.S.Rittmaster (2004).
Dutasteride, the dual 5alpha-reductase inhibitor, inhibits androgen action and promotes cell death in the LNCaP prostate cancer cell line.
  Prostate, 58, 130-144.  
15328534 E.Hur, S.J.Pfaff, E.S.Payne, H.Grøn, B.M.Buehrer, and R.J.Fletterick (2004).
Recognition and accommodation at the androgen receptor coactivator binding interface.
  PLoS Biol, 2, E274.
PDB codes: 1t73 1t74 1t76 1t79 1t7f 1t7m 1t7r 1t7t
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.  
15109611 P.J.Fuller (2004).
Aldosterone and DNA: the 50th anniversary.
  Trends Endocrinol Metab, 15, 143-146.  
14517908 A.Nayeem, S.Krystek, and T.Stouch (2003).
An assessment of protein-ligand binding site polarizability.
  Biopolymers, 70, 201-211.  
12612084 B.He, and E.M.Wilson (2003).
Electrostatic modulation in steroid receptor recruitment of LXXLL and FXXLF motifs.
  Mol Cell Biol, 23, 2135-2150.  
16604181 G.F.Allan, and Z.Sui (2003).
Therapeutic androgen receptor ligands.
  Nucl Recept Signal, 1, e009.  
  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.  
12588987 L.N.Song, R.Herrell, S.Byers, S.Shah, E.M.Wilson, and E.P.Gelmann (2003).
Beta-catenin binds to the activation function 2 region of the androgen receptor and modulates the effects of the N-terminal domain and TIF2 on ligand-dependent transcription.
  Mol Cell Biol, 23, 1674-1687.  
12970085 R.J.Naftalin, I.Afzal, P.Cunningham, M.Halai, C.Ross, N.Salleh, and S.R.Milligan (2003).
Interactions of androgens, green tea catechins and the antiandrogen flutamide with the external glucose-binding site of the human erythrocyte glucose transporter GLUT1.
  Br J Pharmacol, 140, 487-499.  
12682377 S.D.Mooney, T.E.Klein, R.B.Altman, M.A.Trifiro, and B.Gottlieb (2003).
A functional analysis of disease-associated mutations in the androgen receptor gene.
  Nucleic Acids Res, 31, e42.  
12964159 S.S.Muddana, and B.R.Peterson (2003).
Fluorescent cellular sensors of steroid receptor ligands.
  Chembiochem, 4, 848-855.  
12424754 S.Yamada, M.Shimizu, and K.Yamamoto (2003).
Structure-function relationships of vitamin D including ligand recognition by the vitamin D receptor.
  Med Res Rev, 23, 89.  
12519373 Y.Z.Gad, I.Mazen, S.Lumbroso, S.A.Temtamy, and C.Sultan (2003).
A novel point mutation of the androgen receptor (F804L) in an Egyptian newborn with complete androgen insensitivity associated with congenital glaucoma and hypertrophic pyloric stenosis.
  Clin Genet, 63, 59-63.  
12223047 I.K.Mellinghoff, and C.L.Sawyers (2002).
The emergence of resistance to targeted cancer therapeutics.
  Pharmacogenomics, 3, 603-623.  
12115546 K.Steketee, L.Timmerman, A.C.Ziel-van der Made, P.Doesburg, A.O.Brinkmann, and J.Trapman (2002).
Broadened ligand responsiveness of androgen receptor mutants obtained by random amino acid substitution of H874 and mutation hot spot T877 in prostate cancer.
  Int J Cancer, 100, 309-317.  
11931767 Y.Shang, M.Myers, and M.Brown (2002).
Formation of the androgen receptor transcription complex.
  Mol Cell, 9, 601-610.  
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. Where a reference describes a PDB structure, the PDB code is shown on the right.

 

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