3KCX

Factor inhibiting HIF-1 alpha in complex with Clioquinol


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.292 
  • R-Value Work: 0.244 
  • R-Value Observed: 0.246 

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Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Crystal structures of human FIH-1 in complex with quinol family inhibitors

Moon, H.Han, S.Park, H.Choe, J.

(2010) Mol Cells 29: 471-474

  • DOI: https://doi.org/10.1007/s10059-010-0058-3
  • Primary Citation of Related Structures:  
    3KCX, 3KCY

  • PubMed Abstract: 

    Hypoxia-Inducible Factor-1 (HIF-1) plays an important role as a transcription factor under hypoxia. It activates numerous genes including those involved in angiogenesis, glucose metabolisms, cell proliferation and cell survival. The HIF-1 alpha subunit is regulated by 2-oxoglutarate (OG)- and Fe(II)-dependent hydroxylases, including Factor Inhibiting HIF-1 (FIH-1). FIH-1 hydroxylates Asn803 of HIF-1 alpha and blocks its interaction with co-activating molecules. Quinol family compounds such as 5-chloro-7-iodo-8-hydroxyquinoline (Clioquinol) have been shown to inhibit the hydroxylation activity of FIH-1. Here we determined the complex crystal structures of FIH-1: Clioquinol and FIH-1: 8-Hydroxyquinoline. Clioquinol and 8-Hydroxyquinoline bind to the active site of FIH-1 by coordinating the Fe(II) ion, thereby inhibiting the binding of a co-substrate, 2OG. Contrary to other known FIH-1 inhibitors that have negative charges, Clioquinol and 8-hydroxyquinoline are neutral in charge and can provide a template for improved inhibitor design that can selectively inhibit FIH-1.


  • Organizational Affiliation

    Department of Life Science, University of Seoul, Seoul 130-743, Korea.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Hypoxia-inducible factor 1-alpha inhibitor335Homo sapiensMutation(s): 0 
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
Expand
  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
CQL
Query on CQL

Download Ideal Coordinates CCD File 
H [auth A]5-chloro-7-iodoquinolin-8-ol
C9 H5 Cl I N O
QCDFBFJGMNKBDO-UHFFFAOYSA-N
SO4
Query on SO4

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

Download Ideal Coordinates CCD File 
E [auth A],
F [auth A],
G [auth A]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
FE2
Query on FE2

Download Ideal Coordinates CCD File 
B [auth A]FE (II) ION
Fe
CWYNVVGOOAEACU-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.292 
  • R-Value Work: 0.244 
  • R-Value Observed: 0.246 
  • Space Group: P 41 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 86.746α = 90
b = 86.746β = 90
c = 146.525γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
REFMACrefinement
PDB_EXTRACTdata extraction

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-04-28
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2014-02-26
    Changes: Database references
  • Version 1.3: 2017-11-01
    Changes: Refinement description
  • Version 1.4: 2024-03-20
    Changes: Data collection, Database references, Derived calculations