1LQB

Crystal structure of a hydroxylated HIF-1 alpha peptide bound to the pVHL/elongin-C/elongin-B complex


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.277 
  • R-Value Work: 0.225 
  • R-Value Observed: 0.225 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Structural basis for the recognition of hydroxyproline in HIF-1 alpha by pVHL.

Hon, W.C.Wilson, M.I.Harlos, K.Claridge, T.D.Schofield, C.J.Pugh, C.W.Maxwell, P.H.Ratcliffe, P.J.Stuart, D.I.Jones, E.Y.

(2002) Nature 417: 975-978

  • DOI: https://doi.org/10.1038/nature00767
  • Primary Citation of Related Structures:  
    1LQB

  • PubMed Abstract: 

    Hypoxia-inducible factor-1 (HIF-1) is a transcriptional complex that controls cellular and systemic homeostatic responses to oxygen availability. HIF-1 alpha is the oxygen-regulated subunit of HIF-1, an alpha beta heterodimeric complex. HIF-1 alpha is stable in hypoxia, but in the presence of oxygen it is targeted for proteasomal degradation by the ubiquitination complex pVHL, the protein of the von Hippel Lindau (VHL) tumour suppressor gene and a component of an E3 ubiquitin ligase complex. Capture of HIF-1 alpha by pVHL is regulated by hydroxylation of specific prolyl residues in two functionally independent regions of HIF-1 alpha. The crystal structure of a hydroxylated HIF-1 alpha peptide bound to VCB (pVHL, elongins C and B) and solution binding assays reveal a single, conserved hydroxyproline-binding pocket in pVHL. Optimized hydrogen bonding to the buried hydroxyprolyl group confers precise discrimination between hydroxylated and unmodified prolyl residues. This mechanism provides a new focus for development of therapeutic agents to modulate cellular responses to hypoxia.


  • Organizational Affiliation

    Division of Structural Biology, Henry Wellcome Building of Genomic Medicine, Roosevelt Drive, Oxford OX3 7BN, UK.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Elongin B118Homo sapiensMutation(s): 0 
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PHAROS:  Q15370
GTEx:  ENSG00000103363 
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UniProt GroupQ15370
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Elongin C96Homo sapiensMutation(s): 0 
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Find proteins for Q15369 (Homo sapiens)
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GTEx:  ENSG00000154582 
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UniProt GroupQ15369
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
von hippel-lindau disease tumor supressor162Homo sapiensMutation(s): 0 
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Find proteins for P40337 (Homo sapiens)
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PHAROS:  P40337
GTEx:  ENSG00000134086 
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UniProt GroupP40337
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Entity ID: 4
MoleculeChains Sequence LengthOrganismDetailsImage
Hypoxia-inducible factor 1 ALPHA34N/AMutation(s): 1 
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Find proteins for Q16665 (Homo sapiens)
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PHAROS:  Q16665
GTEx:  ENSG00000100644 
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UniProt GroupQ16665
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
SO4
Query on SO4

Download Ideal Coordinates CCD File 
E [auth A]SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
HYP
Query on HYP
D
L-PEPTIDE LINKINGC5 H9 N O3PRO
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.277 
  • R-Value Work: 0.225 
  • R-Value Observed: 0.225 
  • Space Group: P 43 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 58.94α = 90
b = 58.94β = 90
c = 243.38γ = 90
Software Package:
Software NamePurpose
EPMRphasing
CNSrefinement
HKL-2000data reduction
SCALEPACKdata scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2002-07-03
    Type: Initial release
  • Version 1.1: 2008-04-28
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2023-08-16
    Changes: Data collection, Database references, Derived calculations, Refinement description