RCSB PDB - 6QGV: HIF prolyl hydroxylase 2 (PHD2/ EGLN1) in complex with a Spiro[4.5]decanone inhibitor (JPHM-2-167)

 6QGV

HIF prolyl hydroxylase 2 (PHD2/ EGLN1) in complex with a Spiro[4.5]decanone inhibitor (JPHM-2-167)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.40 Å
  • R-Value Free: 0.172 
  • R-Value Work: 0.157 
  • R-Value Observed: 0.158 

Starting Model: experimental
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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 J2HClick on this verticalbar to view details

This is version 1.3 of the entry. See complete history


Literature

Studies on spiro[4.5]decanone prolyl hydroxylase domain inhibitors.

Holt-Martyn, J.P.Tumber, A.Rahman, M.Z.Lippl, K.Figg Jr., W.McDonough, M.A.Chowdhury, R.Schofield, C.J.

(2019) Medchemcomm 10: 500-504

  • DOI: https://doi.org/10.1039/c8md00548f
  • Primary Citation of Related Structures:  
    6QGV

  • PubMed Abstract: 

    The 2-oxoglutarate (2OG) dependent hypoxia inducible factor (HIF) prolyl hydroxylases (PHDs) are targets for treatment of anaemia and other ischaemia related diseases. PHD inhibitors are in clinical trials; however, the number of reported templates for PHD inhibition is limited. We report structure-activity relationship and crystallographic studies on spiro[4.5]decanone containing PHD inhibitors. Together with other studies, our results reveal spiro[4.5]decanones as useful templates for generation of potent and selective 2OG oxygenase inhibitors.


  • Organizational Affiliation

    Department of Chemistry , University of Oxford , Chemistry Research Laboratory , 12 Mansfield Road , Oxford , OX1 3TA , UK . Email: christopher.schofield@chem.ox.ac.uk.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Egl nine homolog 1233Homo sapiensMutation(s): 0 
Gene Names: EGLN1C1orf12PNAS-118PNAS-137
EC: 1.14.11.29
UniProt & NIH Common Fund Data Resources
Find proteins for Q9GZT9 (Homo sapiens)
Explore Q9GZT9 
Go to UniProtKB:  Q9GZT9
PHAROS:  Q9GZT9
GTEx:  ENSG00000135766 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9GZT9
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 5 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
J2H
Query on J2H

Download Ideal Coordinates CCD File 
C [auth A]8-[(3-methylpyridin-2-yl)methyl]-3-(4-phenylphenyl)-1-pyrimidin-2-yl-1,3,8-triazaspiro[4.5]decane-2,4-dione
C30 H28 N6 O2
FIMHRJKSKVXMEB-UHFFFAOYSA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
F [auth A],
G [auth A]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
GOL
Query on GOL

Download Ideal Coordinates CCD File 
D [auth A]GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
IPA
Query on IPA

Download Ideal Coordinates CCD File 
E [auth A]ISOPROPYL ALCOHOL
C3 H8 O
KFZMGEQAYNKOFK-UHFFFAOYSA-N
MN
Query on MN

Download Ideal Coordinates CCD File 
B [auth A]MANGANESE (II) ION
Mn
WAEMQWOKJMHJLA-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
J2H BindingDB:  6QGV IC50: 2.1 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.40 Å
  • R-Value Free: 0.172 
  • R-Value Work: 0.157 
  • R-Value Observed: 0.158 
  • Space Group: H 3 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 120.065α = 90
b = 120.065β = 90
c = 86.563γ = 120
Software Package:
Software NamePurpose
PHENIXrefinement
DIALSdata reduction
SCALAdata scaling
PHASERphasing

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 J2HClick on this verticalbar to view details

Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2020-02-05
    Type: Initial release
  • Version 1.1: 2021-01-20
    Changes: Database references, Refinement description
  • Version 1.2: 2021-02-24
    Changes: Database references
  • Version 1.3: 2024-01-24
    Changes: Data collection, Database references, Refinement description