4IA2

Diastereotopic and Deuterium Effects in Gemini


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.95 Å
  • R-Value Free: 0.256 
  • R-Value Work: 0.204 
  • R-Value Observed: 0.204 

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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Diastereotopic and deuterium effects in gemini.

Maehr, H.Rochel, N.Lee, H.J.Suh, N.Uskokovic, M.R.

(2013) J Med Chem 56: 3878-3888

  • DOI: https://doi.org/10.1021/jm400032t
  • Primary Citation of Related Structures:  
    4IA1, 4IA2, 4IA3, 4IA7

  • PubMed Abstract: 

    Changing the geminal methyl groups on 1α,25-dihydroxyvitamin D3 and its analogues to the deuterio versions generally improves the bioactivity. Derivatives of 1α,25-dihydroxyvitamin D3 with two chains emanating at C20, commonly referred to as gemini, are subject to the same phenomenon. Additionally, gemini with different side chains are susceptible to bioactivity differentials where the C17-C20 threo configuration usually imparts higher activity than the corresponding erythro arrangement. In an effort to analyze the deuterium effect on gemini with minimal diastereotopic distortion, we synthesized gemini with equal side chains but introduced deuterium diastereospecifically on either chain. We solved the crystal structures of these compounds in the zebra fish zVDR ligand binding domain as complexes with NCoA-2 coactivator peptide and correlated the findings with growth inhibition in a breast cancer cell line.


  • Organizational Affiliation

    Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 164 Frelinghuysen Road, Piscataway, New Jersey 08854, USA. hubert.maehr@verizon.net


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 213Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for Q15596 (Homo sapiens)
Explore Q15596 
Go to UniProtKB:  Q15596
PHAROS:  Q15596
GTEx:  ENSG00000140396 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ15596
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
BIV
Query on BIV

Download Ideal Coordinates CCD File 
C [auth A]21-NOR-9,10-SECOCHOLESTA-5,7,10(19)-TRIENE-1,3,25-TRIOL, 20-(4-HYDROXY-4-METHYLPENTYL)-, (1A,3B,5Z,7E)
C32 H54 O4
WTQXZYVWLNPNEX-LKUPKUSPSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.95 Å
  • R-Value Free: 0.256 
  • R-Value Work: 0.204 
  • R-Value Observed: 0.204 
  • Space Group: P 65 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 65.77α = 90
b = 65.77β = 90
c = 266.421γ = 120
Software Package:
Software NamePurpose
CNSrefinement
HKL-2000data reduction
HKL-2000data scaling
CNSphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-04-24
    Type: Initial release
  • Version 1.1: 2013-07-10
    Changes: Database references
  • Version 1.2: 2024-02-28
    Changes: Data collection, Database references, Derived calculations