4BIS

JMJD2A COMPLEXED WITH 8-HYDROXYQUINOLINE-4-CARBOXYLIC ACID

4BIS の概要

• エントリーDOI: 10.2210/pdb4bis/pdb
• 関連するPDBエントリー: 3NJY 4BIO
• 分子名称: LYSINE-SPECIFIC DEMETHYLASE 4A, NICKEL (II) ION, ZINC ION, ... (7 entities in total)
• 機能のキーワード: oxidoreductase, non-heme, 2-oxoglutarate, dioxygenase, oxygenase, facial triad, metal binding protein, epigenetic and transcription regulation, chromatin regulator, hydroxylation
• 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: 89442.08

構造登録者

Chowdhury, R.,Thinnes, C.,Schofield, C.J. (登録日: 2013-04-12, 公開日: 2014-02-05, 最終更新日: 2023-12-20)

主引用文献

Hopkinson, R.J.,Tumber, A.,Yapp, C.,Chowdhury, R.,Aik, W.,Che, K.H.,Li, X.S.,Kristensen, J.B.L.,King, O.N.F.,Chan, M.C.,Yeoh, K.K.,Choi, H.,Walport, L.J.,Thinnes, C.C.,Bush, J.T.,Lejeune, C.,Rydzik, A.M.,Rose, N.R.,Bagg, E.A.,McDonough, M.A.,Krojer, T.,Yue, W.W.,Ng, S.S.,Olsen, L.,Brennan, P.E.,Oppermann, U.,Muller-Knapp, S.,Klose, R.J.,Ratcliffe, P.J.,Schofield, C.J.,Kawamura, A.
5-Carboxy-8-hydroxyquinoline is a Broad Spectrum 2-Oxoglutarate Oxygenase Inhibitor which Causes Iron Translocation.
Chem Sci, 4:3110-3117, 2013

PubMed Abstract: 2-Oxoglutarate and iron dependent oxygenases are therapeutic targets for human diseases. Using a representative 2OG oxygenase panel, we compare the inhibitory activities of 5-carboxy-8-hydroxyquinoline (IOX1) and 4-carboxy-8-hydroxyquinoline (4C8HQ) with that of two other commonly used 2OG oxygenase inhibitors, -oxalylglycine (NOG) and 2,4-pyridinedicarboxylic acid (2,4-PDCA). The results reveal that IOX1 has a broad spectrum of activity, as demonstrated by the inhibition of transcription factor hydroxylases, representatives of all 2OG dependent histone demethylase subfamilies, nucleic acid demethylases and γ-butyrobetaine hydroxylase. Cellular assays show that, unlike NOG and 2,4-PDCA, IOX1 is active against both cytosolic and nuclear 2OG oxygenases without ester derivatisation. Unexpectedly, crystallographic studies on these oxygenases demonstrate that IOX1, but not 4C8HQ, can cause translocation of the active site metal, revealing a rare example of protein ligand-induced metal movement.

PubMed: 26682036
DOI: 10.1039/C3SC51122G

実験手法

X-RAY DIFFRACTION (2.493 Å)