4AI8

FACTOR INHIBITING HIF-1 ALPHA IN COMPLEX WITH DAMINOZIDE


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.248 
  • R-Value Work: 0.231 
  • R-Value Observed: 0.231 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.5 of the entry. See complete history


Literature

Plant growth regulator daminozide is a selective inhibitor of human KDM2/7 histone demethylases.

Rose, N.R.Woon, E.C.Tumber, A.Walport, L.J.Chowdhury, R.Li, X.S.King, O.N.Lejeune, C.Ng, S.S.Krojer, T.Chan, M.C.Rydzik, A.M.Hopkinson, R.J.Che, K.H.Daniel, M.Strain-Damerell, C.Gileadi, C.Kochan, G.Leung, I.K.Dunford, J.Yeoh, K.K.Ratcliffe, P.J.Burgess-Brown, N.von Delft, F.Muller, S.Marsden, B.Brennan, P.E.McDonough, M.A.Oppermann, U.Klose, R.J.Schofield, C.J.Kawamura, A.

(2012) J Med Chem 55: 6639-6643

  • DOI: https://doi.org/10.1021/jm300677j
  • Primary Citation of Related Structures:  
    4AI8, 4AI9

  • PubMed Abstract: 

    The JmjC oxygenases catalyze the N-demethylation of N(ε)-methyl lysine residues in histones and are current therapeutic targets. A set of human 2-oxoglutarate analogues were screened using a unified assay platform for JmjC demethylases and related oxygenases. Results led to the finding that daminozide (N-(dimethylamino)succinamic acid, 160 Da), a plant growth regulator, selectively inhibits the KDM2/7 JmjC subfamily. Kinetic and crystallographic studies reveal that daminozide chelates the active site metal via its hydrazide carbonyl and dimethylamino groups.


  • Organizational Affiliation

    Epigenetic Regulation of Chromatin Function Group, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, U.K.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
HYPOXIA-INDUCIBLE FACTOR 1-ALPHA INHIBITOR352Homo 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
DZA
Query on DZA

Download Ideal Coordinates CCD File 
J [auth A]DAMINOZIDE
C6 H12 N2 O3
NOQGZXFMHARMLW-UHFFFAOYSA-N
SO4
Query on SO4

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

Download Ideal Coordinates CCD File 
G [auth A],
H [auth A],
I [auth A]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
ZN
Query on ZN

Download Ideal Coordinates CCD File 
K [auth A]ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
DZA PDBBind:  4AI8 IC50: 1.00e+5 (nM) from 1 assay(s)
BindingDB:  4AI8 IC50: 1.00e+5 (nM) from 1 assay(s)
Binding MOAD:  4AI8 IC50: 1.00e+5 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.248 
  • R-Value Work: 0.231 
  • R-Value Observed: 0.231 
  • Space Group: P 41 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 86.757α = 90
b = 86.757β = 90
c = 145.481γ = 90
Software Package:
Software NamePurpose
CNSrefinement
HKL-2000data reduction
HKL-2000data scaling
PHASERphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-10-03
    Type: Initial release
  • Version 1.1: 2018-01-24
    Changes: Database references
  • Version 1.2: 2018-03-07
    Changes: Database references, Source and taxonomy, Structure summary
  • Version 1.3: 2019-01-30
    Changes: Data collection, Experimental preparation
  • Version 1.4: 2019-02-06
    Changes: Data collection, Experimental preparation
  • Version 1.5: 2023-12-20
    Changes: Data collection, Database references, Derived calculations, Other, Refinement description