2WWJ

STRUCTURE OF JMJD2A COMPLEXED WITH INHIBITOR 10A

2WWJ の概要

• エントリーDOI: 10.2210/pdb2wwj/pdb
• 関連するPDBエントリー: 2GF7 2GFA 2GP3 2GP5 2VD7
• 分子名称: LYSINE-SPECIFIC DEMETHYLASE 4A, NICKEL (II) ION, ZINC ION, ... (5 entities in total)
• 機能のキーワード: chromatin regulator, double-stranded beta helix, oxidoreductase, transcription, oxygenase, host-virus interaction, transcription regulation
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 82001.26

構造登録者

Rose, N.R.,Clifton, I.J.,Oppermann, U.,McDonough, M.A.,Schofield, C.J. (登録日: 2009-10-23, 公開日: 2010-03-09, 最終更新日: 2023-12-20)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.6 Å)