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Article (Scientific journals)
5-Carboxy-8-hydroxyquinoline is a Broad Spectrum 2-Oxoglutarate Oxygenase Inhibitor which Causes Iron Translocation.
Hopkinson, Richard J.; Tumber, Anthony; Yapp, Clarence et al.
2013In Chemical Science, 4 (8), p. 3110-3117
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Abstract :
[en] 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, N-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 gamma-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.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Hopkinson, Richard J.
Tumber, Anthony
Yapp, Clarence
Chowdhury, Rasheduzzaman
Aik, Weishen
Che, Ka Hing
Li, Xuan Shirley
Kristensen, Jan B. L.
King, Oliver N. F.
Chan, Mun Chiang
Yeoh, Kar Kheng
Choi, Hwanho
Walport, Louise J.
Thinnes, Cyrille ;  University of Oxford
Bush, Jacob T.
Lejeune, Clarisse
Rydzik, Anna M.
Rose, Nathan R.
Bagg, Eleanor A.
McDonough, Michael A.
Krojer, Tobias
Yue, Wyatt W.
Ng, Stanley S.
Olsen, Lars
Brennan, Paul E.
Oppermann, Udo
Muller-Knapp, Susanne
Klose, Robert J.
Ratcliffe, Peter J.
Schofield, Christopher J.
Kawamura, Akane
More authors (21 more) Less
External co-authors :
yes
Language :
English
Title :
5-Carboxy-8-hydroxyquinoline is a Broad Spectrum 2-Oxoglutarate Oxygenase Inhibitor which Causes Iron Translocation.
Publication date :
2013
Journal title :
Chemical Science
ISSN :
2041-6520
Volume :
4
Issue :
8
Pages :
3110-3117
Peer reviewed :
Peer reviewed
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