6FOD

Vitamin D nuclear receptor complex 1


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.244 
  • R-Value Work: 0.187 
  • R-Value Observed: 0.190 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Aromatic-Based Design of Highly Active and Noncalcemic Vitamin D Receptor Agonists.

Gogoi, P.Seoane, S.Sigueiro, R.Guiberteau, T.Maestro, M.A.Perez-Fernandez, R.Rochel, N.Mourino, A.

(2018) J Med Chem 61: 4928-4937

  • DOI: https://doi.org/10.1021/acs.jmedchem.8b00337
  • Primary Citation of Related Structures:  
    6FO7, 6FO8, 6FO9, 6FOB, 6FOD

  • PubMed Abstract: 

    We report the design, synthesis, biological evaluation, and structural analysis of a new class of vitamin D analogues that possess an aromatic m-phenylene D-ring and an alkyl chain replacing the C-ring. A key feature of the synthetic strategy is a stereoselective Pd-catalyzed construction of the triene system in aqueous medium that allows the rapid preparation of small amounts of VDR ligands for biological screening. Analogues with the shorter (2a) and longer (2d, 2e) side chains attached to the triene system have no calcemic activity. Compound 2a binds to VDR with the same order of magnitude than calcipotriol and oxacalcitriol. It also reduces proliferation in normal and tumor cells similarly to the natural hormone 1α,25-dihydroxyvitamin D 3 , calcipotriol, and oxacalcitriol, suggesting preclinical studies related to hyperproliferative disorders such as psoriasis and cancer.


  • Organizational Affiliation

    Department of Organic Chemistry, Research Laboratory Ignacio Ribas , University of Santiago de Compostela , Avenida das Ciencias s/n , 15782 Santiago de Compostela , Spain.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Vitamin D3 receptor A300Danio rerioMutation(s): 0 
Gene Names: vdranr1i1avdr
UniProt
Find proteins for Q9PTN2 (Danio rerio)
Explore Q9PTN2 
Go to UniProtKB:  Q9PTN2
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9PTN2
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Nuclear receptor coactivator 115Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for Q15788 (Homo sapiens)
Explore Q15788 
Go to UniProtKB:  Q15788
PHAROS:  Q15788
GTEx:  ENSG00000084676 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ15788
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
E05
Query on E05

Download Ideal Coordinates CCD File 
C [auth A](1~{R},3~{S},5~{Z})-4-methylidene-5-[(~{E})-3-[3-(6-methyl-6-oxidanyl-heptyl)phenyl]pent-2-enylidene]cyclohexane-1,3-diol
C26 H38 O3
BQVXPWDQMUNMLU-FIKMVKLPSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
E05 Binding MOAD:  6FOD IC50: 7.11 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.244 
  • R-Value Work: 0.187 
  • R-Value Observed: 0.190 
  • Space Group: P 65 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 65.93α = 90
b = 65.93β = 90
c = 264.2γ = 120
Software Package:
Software NamePurpose
BUSTERrefinement
HKL-2000data reduction
HKL-2000data scaling
PHENIXphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data

  • Released Date: 2018-05-16 
  • Deposition Author(s): Rochel, N.

Funding OrganizationLocationGrant Number
French National Research AgencyFranceANR-13-BSV8-0024-01
Spanish Ministry of Economy and CompetitivenessSpainSAF2015-69221-R

Revision History  (Full details and data files)

  • Version 1.0: 2018-05-16
    Type: Initial release
  • Version 1.1: 2018-06-27
    Changes: Data collection, Database references
  • Version 1.2: 2021-02-24
    Changes: Derived calculations
  • Version 1.3: 2024-01-17
    Changes: Advisory, Data collection, Database references, Refinement description