4BIS

JMJD2A COMPLEXED WITH 8-HYDROXYQUINOLINE-4-CARBOXYLIC ACID

Summary for 4BIS

• Entry DOI: 10.2210/pdb4bis/pdb
• Related: 3NJY 4BIO
• Descriptor: LYSINE-SPECIFIC DEMETHYLASE 4A, NICKEL (II) ION, ZINC ION, ... (7 entities in total)
• Functional Keywords: oxidoreductase, non-heme, 2-oxoglutarate, dioxygenase, oxygenase, facial triad, metal binding protein, epigenetic and transcription regulation, chromatin regulator, hydroxylation
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 2
• Total formula weight: 89442.08

Authors

Chowdhury, R.,Thinnes, C.,Schofield, C.J. (deposition date: 2013-04-12, release date: 2014-02-05, Last modification date: 2023-12-20)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.493 Å)