PDBsum entry 2wwj

Go to PDB code: 
protein ligands metals Protein-protein interface(s) links
Oxidoreductase PDB id
Jmol PyMol
Protein chains
346 a.a. *
Y28 ×2
_ZN ×2
_NI ×2
Waters ×144
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: Structure of jmjd2a complexed with inhibitor 10a
Structure: Lysine-specific demethylase 4a. Chain: a, b. Fragment: residues 7-353. Synonym: jumonji domain containing protein 2a, jmjc domain-containing histone demethylation protein 3a. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 469008.
2.60Å     R-factor:   0.181     R-free:   0.247
Authors: N.R.Rose,I.J.Clifton,U.Oppermann,M.A.Mcdonough, C.J.Schofield
Key ref: N.R.Rose et al. (2010). Selective inhibitors of the JMJD2 histone demethylases: combined nondenaturing mass spectrometric screening and crystallographic approaches. J Med Chem, 53, 1810-1818. PubMed id: 20088513
23-Oct-09     Release date:   09-Mar-10    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
O75164  (KDM4A_HUMAN) -  Lysine-specific demethylase 4A
1064 a.a.
346 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - [Histone H3]-lysine-36 demethylase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
1. Protein N6,N6-dimethyl-L-lysine + 2-oxoglutarate + O2 = protein N6-methyl-L-lysine + succinate + formaldehyde + CO2
2. Protein N6-methyl-L-lysine + 2-oxoglutarate + O2 = protein L-lysine + succinate + formaldehyde + CO2
Protein N(6),N(6)-dimethyl-L-lysine
+ 2-oxoglutarate
+ O(2)
= protein N(6)-methyl-L-lysine
+ succinate
+ formaldehyde
+ CO(2)
Protein N(6)-methyl-L-lysine
+ 2-oxoglutarate
+ O(2)
= protein L-lysine
+ succinate
+ formaldehyde
+ CO(2)
      Cofactor: Fe(2+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site


J Med Chem 53:1810-1818 (2010)
PubMed id: 20088513  
Selective inhibitors of the JMJD2 histone demethylases: combined nondenaturing mass spectrometric screening and crystallographic approaches.
N.R.Rose, E.C.Woon, G.L.Kingham, O.N.King, J.Mecinović, I.J.Clifton, S.S.Ng, J.Talib-Hardy, U.Oppermann, M.A.McDonough, C.J.Schofield.
Ferrous ion and 2-oxoglutarate (2OG) oxygenases catalyze the demethylation of N(epsilon)-methylated lysine residues in histones. Here we report studies on the inhibition of the JMJD2 subfamily of histone demethylases, employing binding analyses by nondenaturing mass spectrometry (MS), dynamic combinatorial chemistry coupled to MS, turnover assays, and crystallography. The results of initial binding and inhibition assays directed the production and analysis of a set of N-oxalyl-d-tyrosine derivatives to explore the extent of a subpocket at the JMJD2 active site. Some of the inhibitors were shown to be selective for JMJD2 over the hypoxia-inducible factor prolyl hydroxylase PHD2. A crystal structure of JMJD2A in complex with one of the potent inhibitors was obtained; modeling other inhibitors based on this structure predicts interactions that enable improved inhibition for some compounds.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21076780 A.Thalhammer, J.Mecinović, C.Loenarz, A.Tumber, N.R.Rose, T.D.Heightman, and C.J.Schofield (2011).
Inhibition of the histone demethylase JMJD2E by 3-substituted pyridine 2,4-dicarboxylates.
  Org Biomol Chem, 9, 127-135.  
  21412984 K.H.Chang, O.N.King, A.Tumber, E.C.Woon, T.D.Heightman, M.A.McDonough, C.J.Schofield, and N.R.Rose (2011).
Inhibition of histone demethylases by 4-carboxy-2,2'-bipyridyl compounds.
  ChemMedChem, 6, 759-764.
PDB code: 3pdq
20951770 R.A.Varier, and H.T.Timmers (2011).
Histone lysine methylation and demethylation pathways in cancer.
  Biochim Biophys Acta, 1815, 75-89.  
21243713 S.Krishnan, S.Horowitz, and R.C.Trievel (2011).
Structure and function of histone H3 lysine 9 methyltransferases and demethylases.
  Chembiochem, 12, 254-263.  
21124847 O.N.King, X.S.Li, M.Sakurai, A.Kawamura, N.R.Rose, S.S.Ng, A.M.Quinn, G.Rai, B.T.Mott, P.Beswick, R.J.Klose, U.Oppermann, A.Jadhav, T.D.Heightman, D.J.Maloney, C.J.Schofield, and A.Simeonov (2010).
Quantitative high-throughput screening identifies 8-hydroxyquinolines as cell-active histone demethylase inhibitors.
  PLoS One, 5, e15535.
PDB code: 3njy
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.