RCSB PDB - 4OH6: Crystal structure of T877A-AR-LBD bound with co-regulator peptide

 4OH6

Crystal structure of T877A-AR-LBD bound with co-regulator peptide


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.56 Å
  • R-Value Free: 0.261 
  • R-Value Work: 0.158 
  • R-Value Observed: 0.163 

Starting Model: experimental
View more details

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 

Created with Raphaël 2.3.0Worse 01 BetterLigand structure goodness of fit to experimental dataBest fitted HFTClick on this verticalbar to view details

This is version 1.2 of the entry. See complete history


Literature

Identification of a new androgen receptor (AR) co-regulator BUD31 and related peptides to suppress wild-type and mutated AR-mediated prostate cancer growth via peptide screening and X-ray structure analysis.

Hsu, C.L.Liu, J.S.Wu, P.L.Guan, H.H.Chen, Y.L.Lin, A.C.Ting, H.J.Pang, S.T.Yeh, S.D.Ma, W.L.Chen, C.J.Wu, W.G.Chang, C.

(2014) Mol Oncol 8: 1575-1587

  • DOI: https://doi.org/10.1016/j.molonc.2014.06.009
  • Primary Citation of Related Structures:  
    4OEA, 4OED, 4OEY, 4OEZ, 4OFR, 4OFU, 4OGH, 4OH5, 4OH6, 4OHA, 4OIL, 4OIU, 4OJ9, 4OJB, 4OK1, 4OKB, 4OKT, 4OKW, 4OKX, 4OLM

  • PubMed Abstract: 

    Treatment with individual anti-androgens is associated with the development of hot-spot mutations in the androgen receptor (AR). Here, we found that anti-androgens-mt-ARs have similar binary structure to the 5α-dihydrotestosterone-wt-AR. Phage display revealed that these ARs bound to similar peptides, including BUD31, containing an Fxx(F/H/L/W/Y)Y motif cluster with Tyr in the +5 position. Structural analyses of the AR-LBD-BUD31 complex revealed formation of an extra hydrogen bond between the Tyr+5 residue of the peptide and the AR. Functional studies showed that BUD31-related peptides suppressed AR transactivation, interrupted AR N-C interaction, and suppressed AR-mediated cell growth. Combination of peptide screening and X-ray structure analysis may serve as a new strategy for developing anti-ARs that simultaneously suppress both wt and mutated AR function.


  • Organizational Affiliation

    The George Whipple Lab for Cancer Research, Department of Pathology and Urology, University of Rochester Medical Center, Rochester, NY 14642, USA; Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan 333, Taiwan.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Androgen receptor250Homo sapiensMutation(s): 2 
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

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Protein BUD31 homolog15Homo sapiensMutation(s): 1 
UniProt & NIH Common Fund Data Resources
Find proteins for P41223 (Homo sapiens)
Explore P41223 
Go to UniProtKB:  P41223
PHAROS:  P41223
GTEx:  ENSG00000106245 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP41223
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
HFT BindingDB:  4OH6 Ki: min: 2, max: 2100 (nM) from 6 assay(s)
IC50: min: 15, max: 3.30e+4 (nM) from 18 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.56 Å
  • R-Value Free: 0.261 
  • R-Value Work: 0.158 
  • R-Value Observed: 0.163 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 55.792α = 90
b = 66.1β = 90
c = 70.225γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
AMoREphasing
REFMACrefinement
HKL-2000data reduction
SCALEPACKdata scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 

Created with Raphaël 2.3.0Worse 01 BetterLigand structure goodness of fit to experimental dataBest fitted HFTClick on this verticalbar to view details

Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2014-08-20
    Type: Initial release
  • Version 1.1: 2014-12-24
    Changes: Database references
  • Version 1.2: 2023-09-20
    Changes: Data collection, Database references, Derived calculations, Refinement description