2AM9

Crystal structure of human androgen receptor ligand binding domain in complex with testosterone


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.64 Å
  • R-Value Free: 0.230 
  • R-Value Work: 0.191 
  • R-Value Observed: 0.199 

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This is version 1.2 of the entry. See complete history


Literature

Comparison of crystal structures of human androgen receptor ligand-binding domain complexed with various agonists reveals molecular determinants responsible for binding affinity.

Pereira de Jesus-Tran, K.Cote, P.-L.Cantin, L.Blanchet, J.Labrie, F.Breton, R.

(2006) Protein Sci 15: 987-999

  • DOI: https://doi.org/10.1110/ps.051905906
  • Primary Citation of Related Structures:  
    2AM9, 2AMA, 2AMB

  • PubMed Abstract: 

    Androgens exert their effects by binding to the highly specific androgen receptor (AR). In addition to natural potent androgens, AR binds a variety of synthetic agonist or antagonist molecules with different affinities. To identify molecular determinants responsible for this selectivity, we have determined the crystal structure of the human androgen receptor ligand-binding domain (hARLBD) in complex with two natural androgens, testosterone (Testo) and dihydrotestosterone (DHT), and with an androgenic steroid used in sport doping, tetrahydrogestrinone (THG), at 1.64, 1.90, and 1.75 A resolution, respectively. Comparison of these structures first highlights the flexibility of several residues buried in the ligand-binding pocket that can accommodate a variety of ligand structures. As expected, the ligand structure itself (dimension, presence, and position of unsaturated bonds that influence the geometry of the steroidal nucleus or the electronic properties of the neighboring atoms, etc.) determines the number of interactions it can make with the hARLBD. Indeed, THG--which possesses the highest affinity--establishes more van der Waals contacts with the receptor than the other steroids, whereas the geometry of the atoms forming electrostatic interactions at both extremities of the steroid nucleus seems mainly responsible for the higher affinity measured experimentally for DHT over Testo. Moreover, estimation of the ligand-receptor interaction energy through modeling confirms that even minor modifications in ligand structure have a great impact on the strength of these interactions. Our crystallographic data combined with those obtained by modeling will be helpful in the design of novel molecules with stronger affinity for the AR.


  • Organizational Affiliation

    Oncology and Molecular Endocrinology Research Center, Laval University Medical Center (CHUL) and Laval University, Québec, QC G1V 4G2, Canada.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Androgen receptor266Homo sapiensMutation(s): 0 
Gene Names: ARDHTRNR3C4
UniProt & NIH Common Fund Data Resources
Find proteins for P10275 (Homo sapiens)
Explore P10275 
Go to UniProtKB:  P10275
PHAROS:  P10275
GTEx:  ENSG00000169083 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP10275
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
TES BindingDB:  2AM9 Ki: min: 1.4, max: 29 (nM) from 5 assay(s)
IC50: min: 2.7, max: 3090.3 (nM) from 11 assay(s)
EC50: min: 1.1, max: 3.16 (nM) from 3 assay(s)
PDBBind:  2AM9 IC50: 3.9 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.64 Å
  • R-Value Free: 0.230 
  • R-Value Work: 0.191 
  • R-Value Observed: 0.199 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 53.82α = 90
b = 65.92β = 90
c = 71.04γ = 90
Software Package:
Software NamePurpose
XSCALEdata processing
CNSrefinement
PDB_EXTRACTdata extraction
CrystalCleardata reduction
XSCALEdata scaling
AMoREphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2006-05-16
    Type: Initial release
  • Version 1.1: 2008-04-30
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Non-polymer description, Version format compliance