5L9B

HIF PROLYL HYDROXYLASE 2 (PHD2/ EGLN1) IN COMPLEX WITH 2-OXOGLUTARATE (2OG) AND HIF-1ALPHA CODD (556-574)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.95 Å
  • R-Value Free: 0.186 
  • R-Value Work: 0.157 
  • R-Value Observed: 0.161 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Structural basis for oxygen degradation domain selectivity of the HIF prolyl hydroxylases.

Chowdhury, R.Leung, I.K.Tian, Y.M.Abboud, M.I.Ge, W.Domene, C.Cantrelle, F.X.Landrieu, I.Hardy, A.P.Pugh, C.W.Ratcliffe, P.J.Claridge, T.D.Schofield, C.J.

(2016) Nat Commun 7: 12673-12673

  • DOI: https://doi.org/10.1038/ncomms12673
  • Primary Citation of Related Structures:  
    5L9B, 5L9R, 5L9V, 5LA9, 5LAS, 5LAT, 5LB6, 5LBB, 5LBC, 5LBE, 5LBF

  • PubMed Abstract: 

    The response to hypoxia in animals involves the expression of multiple genes regulated by the αβ-hypoxia-inducible transcription factors (HIFs). The hypoxia-sensing mechanism involves oxygen limited hydroxylation of prolyl residues in the N- and C-terminal oxygen-dependent degradation domains (NODD and CODD) of HIFα isoforms, as catalysed by prolyl hydroxylases (PHD 1-3). Prolyl hydroxylation promotes binding of HIFα to the von Hippel-Lindau protein (VHL)-elongin B/C complex, thus signalling for proteosomal degradation of HIFα. We reveal that certain PHD2 variants linked to familial erythrocytosis and cancer are highly selective for CODD or NODD. Crystalline and solution state studies coupled to kinetic and cellular analyses reveal how wild-type and variant PHDs achieve ODD selectivity via different dynamic interactions involving loop and C-terminal regions. The results inform on how HIF target gene selectivity is achieved and will be of use in developing selective PHD inhibitors.


  • Organizational Affiliation

    Chemistry Research Laboratory, Department of Chemistry, Oxford Centre for Integrative Systems Biology, University of Oxford, 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
252Homo sapiensMutation(s): 2 
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

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Hypoxia-inducible factor 1-alpha
C, D
19Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for Q16665 (Homo sapiens)
Explore Q16665 
Go to UniProtKB:  Q16665
PHAROS:  Q16665
GTEx:  ENSG00000100644 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ16665
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.95 Å
  • R-Value Free: 0.186 
  • R-Value Work: 0.157 
  • R-Value Observed: 0.161 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 40.193α = 90
b = 76.395β = 90.03
c = 70.962γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-2000data reduction
HKL-2000data scaling
PHASERphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2016-08-31
    Type: Initial release
  • Version 1.1: 2016-09-07
    Changes: Database references
  • Version 1.2: 2024-01-10
    Changes: Data collection, Database references, Derived calculations, Refinement description