6ST3

HIF prolyl hydroxylase 2 (PHD2/ EGLN1) in complex with 4-hydroxy-N-(4-phenoxybenzyl)-2-(1H-pyrazol-1-yl)pyrimidine-5-carboxamide

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.43 Å
  • R-Value Free: 0.217 
  • R-Value Work: 0.192 
  • R-Value Observed: 0.194 

Starting Model: experimental
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This is version 1.2 of the entry. See complete history. 


Literature

Structure-Activity Relationship and Crystallographic Studies on 4-Hydroxypyrimidine HIF Prolyl Hydroxylase Domain Inhibitors.

Holt-Martyn, J.P., Chowdhury, R., Tumber, A., Yeh, T.L., Abboud, M.I., Lippl, K., Lohans, C.T., Langley, G.W., Figg Jr., W., McDonough, M.A., Pugh, C.W., Ratcliffe, P.J., Schofield, C.J.

(2020) ChemMedChem 15: 270-273

  • DOI: https://doi.org/10.1002/cmdc.201900557
  • Primary Citation of Related Structures:  
    6ST3

  • PubMed Abstract: 

    The 2-oxoglutarate-dependent hypoxia inducible factor prolyl hydroxylases (PHDs) are targets for treatment of a variety of diseases including anaemia. One PHD inhibitor is approved for use for the treatment of renal anaemia and others are in late stage clinical trials. The number of reported templates for PHD inhibition is limited. We report structure-activity relationship and crystallographic studies on a promising class of 4-hydroxypyrimidine-containing PHD inhibitors.

    • Organizational Affiliation: 

    Department of Chemistry, University of Oxford Chemistry Research Laboratory, 12 Mansfield Road, Oxford, OX1 3TA, UK.


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Egl nine homolog 1
A, B
233Homo sapiensMutation(s): 0 
Gene Names: EGLN1, C1orf12, PNAS-118, PNAS-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 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
LUW (Subject of Investigation/LOI)
Query on LUW
Download Ideal Coordinates CCD File 
C [auth A],
G [auth B]		4-oxidanyl-~{N}-[(4-phenoxyphenyl)methyl]-2-pyrazol-1-yl-pyrimidine-5-carboxamide
C21 H17 N5 O3
WBANHLSPTRNPCR-UHFFFAOYSA-N
MN
Query on MN
Download Ideal Coordinates CCD File 
E [auth A],
F [auth B]		MANGANESE (II) ION
Mn
WAEMQWOKJMHJLA-UHFFFAOYSA-N
FMT
Query on FMT
Download Ideal Coordinates CCD File 
D [auth A],
H [auth B]		FORMIC ACID
C H2 O2
BDAGIHXWWSANSR-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.43 Å
  • R-Value Free: 0.217 
  • R-Value Work: 0.192 
  • R-Value Observed: 0.194 
  • Space Group: P 21 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 72.87α = 90
b = 80.58β = 90
c = 83.92γ = 90
Software Package:
Software NamePurpose
Aimlessdata scaling
PHENIXrefinement
PDB_EXTRACTdata extraction
MOSFLMdata reduction
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2019-12-04
    Type: Initial release
  • Version 1.1: 2020-02-19
    Changes: Database references
  • Version 1.2: 2024-01-24
    Changes: Data collection, Database references, Derived calculations, Refinement description