1YCI

Factor inhibiting HIF-1 alpha in complex with N-(carboxycarbonyl)-D-phenylalanine


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.244 
  • R-Value Work: 0.210 
  • R-Value Observed: 0.210 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Selective inhibition of factor inhibiting hypoxia-inducible factor

McDonough, M.A.McNeill, L.A.Tilliet, M.Papamicael, C.A.Chen, Q.Y.Banerji, B.Hewitson, K.S.Schofield, C.J.

(2005) J Am Chem Soc 127: 7680-7681

  • DOI: https://doi.org/10.1021/ja050841b
  • Primary Citation of Related Structures:  
    1YCI

  • PubMed Abstract: 

    A set of four non-heme iron(II) and 2-oxoglutarate-dependent enzymes catalyze the post-translational modification of a transcription factor, hypoxia inducible factor (HIF), that mediates the hypoxic response in animals. Hydroxylation of HIF both causes its degradation and limits its activity. We describe how the use of structural data coupled to solid-phase synthesis led to the discovery of a selective inhibitor of one of the HIF hydroxylases. The inhibitor N-oxalyl-d-phenylalanine was shown to inhibit the HIF asparaginyl hydroxylase (FIH) but not a HIF prolyl hydroxylase. A crystal structure of the inhibitor complexed to FIH reveals that it binds in the 2OG and, likely, in the dioxygen binding site. The results will help to enable the modulation of the hypoxic response for the up-regulation of specific genes of biomedical importance, such as erythropoietin and vascular endothelial growth factor.


  • Organizational Affiliation

    The Department of Chemistry and The Oxford Centre for Molecular Sciences, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford, OX1 3TA, United Kingdom.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Hypoxia-inducible factor 1 alpha inhibitor349Homo sapiensMutation(s): 0 
Gene Names: HIF1AN
EC: 1.14.11.16
UniProt & NIH Common Fund Data Resources
Find proteins for Q9NWT6 (Homo sapiens)
Explore Q9NWT6 
Go to UniProtKB:  Q9NWT6
PHAROS:  Q9NWT6
GTEx:  ENSG00000166135 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9NWT6
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.244 
  • R-Value Work: 0.210 
  • R-Value Observed: 0.210 
  • Space Group: P 41 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 86.853α = 90
b = 86.853β = 90
c = 150.519γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
CNSrefinement

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2005-05-31
    Type: Initial release
  • Version 1.1: 2008-04-30
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Derived calculations, Version format compliance
  • Version 1.3: 2023-10-25
    Changes: Data collection, Database references, Derived calculations, Refinement description