5FP9

Crystal structure of human KDM4D in complex with 3-aminopyridine-4- carboxylic acid


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.211 
  • R-Value Work: 0.157 
  • R-Value Observed: 0.159 

wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

Cell Penetrant Inhibitors of the Kdm4 and Kdm5 Families of Histone Lysine Demethylases. 1. 3-Amino-4-Pyridine Carboxylate Derivatives.

Westaway, S.M.Preston, A.G.S.Barker, M.D.Brown, F.Brown, J.A.Campbell, M.Chung, C.Diallo, H.Douault, C.Drewes, G.Eagle, R.Gordon, L.Haslam, C.Hayhow, T.G.Humphreys, P.G.Joberty, G.Katso, R.Kruidenier, L.Leveridge, M.Liddle, J.Mosley, J.Muelbaier, M.Randle, R.Rioja, I.Rueger, A.Seal, G.A.Sheppard, R.J.Singh, O.Taylor, J.Thomas, P.Thomson, D.Wilson, D.M.Lee, K.Prinjha, R.K.

(2016) J Med Chem 59: 1357

  • DOI: https://doi.org/10.1021/acs.jmedchem.5b01537
  • Primary Citation of Related Structures:  
    5FP3, 5FP4, 5FP8, 5FP9, 5FPA, 5FPB

  • PubMed Abstract: 

    Optimization of KDM6B (JMJD3) HTS hit 12 led to the identification of 3-((furan-2-ylmethyl)amino)pyridine-4-carboxylic acid 34 and 3-(((3-methylthiophen-2-yl)methyl)amino)pyridine-4-carboxylic acid 39 that are inhibitors of the KDM4 (JMJD2) family of histone lysine demethylases. Compounds 34 and 39 possess activity, IC50 ≤ 100 nM, in KDM4 family biochemical (RFMS) assays with ≥ 50-fold selectivity against KDM6B and activity in a mechanistic KDM4C cell imaging assay (IC50 = 6-8 μM). Compounds 34 and 39 are also potent inhibitors of KDM5C (JARID1C) (RFMS IC50 = 100-125 nM).


  • Organizational Affiliation

    Epinova Discovery Performance Unit, Medicines Research Centre, GlaxoSmithKline R&D , Stevenage SG1 2NY, U.K.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
HUMAN LYSINE-SPECIFIC DEMETHYLASE 4D JMJC DOMAIN-CONTAINING HISTONE DEMETHYLATION PROTEIN 3D, JUMONJI DOMAIN-CONTAINING PROTEIN 2D, JMJD2D334Homo sapiensMutation(s): 0 
EC: 1.14.11
UniProt & NIH Common Fund Data Resources
Find proteins for Q6B0I6 (Homo sapiens)
Explore Q6B0I6 
Go to UniProtKB:  Q6B0I6
PHAROS:  Q6B0I6
GTEx:  ENSG00000186280 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ6B0I6
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 5 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
4SV
Query on 4SV

Download Ideal Coordinates CCD File 
E [auth A]3-AMINOPYRIDINE-4-CARBOXYLIC ACID
C6 H6 N2 O2
FYEQKMAVRYRMBL-UHFFFAOYSA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
F [auth A]
G [auth A]
H [auth A]
I [auth A]
J [auth A]
F [auth A],
G [auth A],
H [auth A],
I [auth A],
J [auth A],
K [auth A],
L [auth A]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
GOL
Query on GOL

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

Download Ideal Coordinates CCD File 
B [auth A]ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
CO
Query on CO

Download Ideal Coordinates CCD File 
C [auth A]COBALT (II) ION
Co
XLJKHNWPARRRJB-UHFFFAOYSA-N
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
CSX
Query on CSX
A
L-PEPTIDE LINKINGC3 H7 N O3 SCYS
Binding Affinity Annotations 
IDSourceBinding Affinity
4SV Binding MOAD:  5FP9 IC50: 1585 (nM) from 1 assay(s)
BindingDB:  5FP9 IC50: min: 1259, max: 1585 (nM) from 2 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.211 
  • R-Value Work: 0.157 
  • R-Value Observed: 0.159 
  • Space Group: P 43 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 71.416α = 90
b = 71.416β = 90
c = 150.292γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
DENZOdata reduction
SCALEPACKdata scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

  • Released Date: 2016-01-27 
  • Deposition Author(s): Chung, C.

Revision History  (Full details and data files)

  • Version 1.0: 2016-01-27
    Type: Initial release
  • Version 1.1: 2016-03-09
    Changes: Database references