6XZJ

Structure of zVDR LBD-Calcitriol in complex with chimera 12


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.247 
  • R-Value Work: 0.202 
  • R-Value Observed: 0.204 

Starting Model: experimental
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Ligand Structure Quality Assessment 


This is version 2.1 of the entry. See complete history


Literature

Structural Basis for alpha-Helix Mimicry and Inhibition of Protein-Protein Interactions with Oligourea Foldamers.

Cussol, L.Mauran-Ambrosino, L.Buratto, J.Belorusova, A.Y.Neuville, M.Osz, J.Fribourg, S.Fremaux, J.Dolain, C.Goudreau, S.R.Rochel, N.Guichard, G.

(2021) Angew Chem Int Ed Engl 60: 2296-2303

  • DOI: https://doi.org/10.1002/anie.202008992
  • Primary Citation of Related Structures:  
    6HFA, 6XZH, 6XZI, 6XZJ, 6XZK, 6XZV

  • PubMed Abstract: 

    Efficient optimization of a peptide lead into a drug candidate frequently needs further transformation to augment properties such as bioavailability. Among the different options, foldamers, which are sequence-based oligomers with precise folded conformation, have emerged as a promising technology. We introduce oligourea foldamers to reduce the peptide character of inhibitors of protein-protein interactions (PPI). However, the precise design of such mimics is currently limited by the lack of structural information on how these foldamers adapt to protein surfaces. We report a collection of X-ray structures of peptide-oligourea hybrids in complex with ubiquitin ligase MDM2 and vitamin D receptor and show how such hybrid oligomers can be designed to bind with high affinity to protein targets. This work should enable the generation of more effective foldamer-based disruptors of PPIs in the context of peptide lead optimization.


  • Organizational Affiliation

    Univ. Bordeaux, CNRS, Bordeaux INP, CBMN, UMR 5248, Institut Européen de Chimie et Biologie, 2 rue Robert Escarpit, F-33607, Pessac, France.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Vitamin D3 receptor A302Danio 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
ARG-HIS-LYS-ILE-LEU-URR-UIL-URL-GLN9synthetic constructMutation(s): 0 
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
VDX
Query on VDX

Download Ideal Coordinates CCD File 
C [auth A]5-{2-[1-(5-HYDROXY-1,5-DIMETHYL-HEXYL)-7A-METHYL-OCTAHYDRO-INDEN-4-YLIDENE]-ETHYLIDENE}-4-METHYLENE-CYCLOHEXANE-1,3-DIOL
C27 H44 O3
GMRQFYUYWCNGIN-NKMMMXOESA-N
ACT
Query on ACT

Download Ideal Coordinates CCD File 
D [auth A]ACETATE ION
C2 H3 O2
QTBSBXVTEAMEQO-UHFFFAOYSA-M
Binding Affinity Annotations 
IDSourceBinding Affinity
VDX BindingDB:  6XZJ Kd: 1200 (nM) from 1 assay(s)
EC50: 5.5 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.247 
  • R-Value Work: 0.202 
  • R-Value Observed: 0.204 
  • Space Group: P 65 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 66.2α = 90
b = 66.2β = 90
c = 254.22γ = 120
Software Package:
Software NamePurpose
PHENIXrefinement
PDB_EXTRACTdata extraction
XDSdata reduction
Aimlessdata scaling
PHENIXphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
French National Research AgencyFrance--

Revision History  (Full details and data files)

  • Version 1.0: 2021-02-17
    Type: Initial release
  • Version 1.1: 2021-09-01
    Changes: Database references
  • Version 2.0: 2023-11-15
    Changes: Atomic model, Data collection, Derived calculations
  • Version 2.1: 2024-01-24
    Changes: Refinement description