1I38

CRYSTAL STRUCTURE OF THE RAT ANDROGEN RECEPTOR LIGAND BINDING DOMAIN T877A MUTANT COMPLEX WITH DIHYDROTESTOSTERONE


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.345 
  • R-Value Work: 0.280 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Crystallographic structures of the ligand-binding domains of the androgen receptor and its T877A mutant complexed with the natural agonist dihydrotestosterone.

Sack, J.S.Kish, K.F.Wang, C.Attar, R.M.Kiefer, S.E.An, Y.Wu, G.Y.Scheffler, J.E.Salvati, M.E.Krystek Jr., S.R.Weinmann, R.Einspahr, H.M.

(2001) Proc Natl Acad Sci U S A 98: 4904-4909

  • DOI: https://doi.org/10.1073/pnas.081565498
  • Primary Citation of Related Structures:  
    1I37, 1I38

  • PubMed 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.


  • Organizational Affiliation

    Bristol-Myers Squibb Pharmaceutical Research Institute, P.O. Box 4000, Princeton, NJ 08543-4000, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
ANDROGEN RECEPTOR260Rattus norvegicusMutation(s): 0 
UniProt
Find proteins for P15207 (Rattus norvegicus)
Explore P15207 
Go to UniProtKB:  P15207
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP15207
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
DHT
Query on DHT

Download Ideal Coordinates CCD File 
B [auth A]5-ALPHA-DIHYDROTESTOSTERONE
C19 H30 O2
NVKAWKQGWWIWPM-ABEVXSGRSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
DHT BindingDB:  1I38 Ki: min: 0.2, max: 10 (nM) from 12 assay(s)
IC50: min: 0.05, max: 18.5 (nM) from 14 assay(s)
EC50: min: 0.05, max: 20 (nM) from 14 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.345 
  • R-Value Work: 0.280 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 56.01α = 90
b = 65.71β = 90
c = 70.77γ = 90
Software Package:
Software NamePurpose
AMoREphasing
CNXrefinement
DENZOdata reduction
SCALEPACKdata scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

  • Released Date: 2001-03-21 
  • Deposition Author(s): Sack, J.S.

Revision History  (Full details and data files)

  • Version 1.0: 2001-03-21
    Type: Initial release
  • Version 1.1: 2008-04-27
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2023-08-09
    Changes: Data collection, Database references, Derived calculations, Refinement description