2WWJ

STRUCTURE OF JMJD2A COMPLEXED WITH INHIBITOR 10A

Summary for 2WWJ

• Entry DOI: 10.2210/pdb2wwj/pdb
• Related: 2GF7 2GFA 2GP3 2GP5 2VD7
• Descriptor: LYSINE-SPECIFIC DEMETHYLASE 4A, NICKEL (II) ION, ZINC ION, ... (5 entities in total)
• Functional Keywords: chromatin regulator, double-stranded beta helix, oxidoreductase, transcription, oxygenase, host-virus interaction, transcription regulation
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 82001.26

Authors

Rose, N.R.,Clifton, I.J.,Oppermann, U.,McDonough, M.A.,Schofield, C.J. (deposition date: 2009-10-23, release date: 2010-03-09, Last modification date: 2023-12-20)

Primary citation

Rose, N.R.,Woon, E.C.,Kingham, G.L.,King, O.N.,Mecinovic, J.,Clifton, I.J.,Ng, S.S.,Talib-Hardy, J.,Oppermann, U.,McDonough, M.A.,Schofield, C.J.
Selective inhibitors of the JMJD2 histone demethylases: combined nondenaturing mass spectrometric screening and crystallographic approaches.
J. Med. Chem., 53:1810-1818, 2010

PubMed Abstract: 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.

PubMed: 20088513
DOI: 10.1021/jm901680b

Experimental method

X-RAY DIFFRACTION (2.6 Å)