4JHT
Crystal Structure of AlkB in complex with 5-carboxy-8-hydroxyquinoline (IOX1)
Summary for 4JHT
| Entry DOI | 10.2210/pdb4jht/pdb |
| Related | 2FDB 2FDF 2FDG 2FDH 2FDI 2FDJ 2FDK 3BI3 3BIE 3BKZ 3H8O 3H8R 3H8X 3I2O 3I3M 3I3Q 3I49 3KHB 3KHC 3O1M 3O1O 3O1P 3O1R 3O1S 3O1T 3O1U 3O1V 3T3Y 3T4H 3T4V |
| Descriptor | Alpha-ketoglutarate-dependent dioxygenase AlkB, 8-hydroxyquinoline-5-carboxylic acid, MANGANESE (II) ION, ... (6 entities in total) |
| Functional Keywords | double-stranded beta helix, jelly-roll motif, oxidoreductase, dioxygenase, nucleic acid demethylase, oxidoreductase-oxidoreductase inhibitor complex, oxidoreductase/oxidoreductase inhibitor |
| Biological source | Escherichia coli |
| Total number of polymer chains | 1 |
| Total formula weight | 23326.52 |
| Authors | Aik, W.S.,McDonough, M.A.,Schofield, C.J. (deposition date: 2013-03-05, release date: 2013-06-26, Last modification date: 2023-11-08) |
| 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 Cited by 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: 26682036DOI: 10.1039/C3SC51122G PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.18 Å) |
Structure validation
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