3T3Y
Crystal structure of AlkB in complex with Fe(III) and 2-(3-hydroxypicolinomido)acetic acid
Summary for 3T3Y
| Entry DOI | 10.2210/pdb3t3y/pdb |
| Related | 2FD8 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 3T4H 3T4V |
| Descriptor | Alpha-ketoglutarate-dependent dioxygenase AlkB, FE (III) ION, N-[(3-hydroxypyridin-2-yl)carbonyl]glycine, ... (4 entities in total) |
| Functional Keywords | double-stranded beta-helix, nucleic acid demethylase, oxidoreductase-oxidoreductase inhibitor complex, oxidoreductase/oxidoreductase inhibitor |
| Biological source | Escherichia coli |
| Total number of polymer chains | 1 |
| Total formula weight | 23197.24 |
| Authors | Aik, W.S.,McDonough, M.A.,Schofield, C.J. (deposition date: 2011-07-25, release date: 2012-03-07, Last modification date: 2023-09-13) |
| Primary citation | Woon, E.C.,Demetriades, M.,Bagg, E.A.,Aik, W.,Krylova, S.M.,Ma, J.H.,Chan, M.,Walport, L.J.,Wegman, D.W.,Dack, K.N.,McDonough, M.A.,Krylov, S.N.,Schofield, C.J. Dynamic combinatorial mass spectrometry leads to inhibitors of a 2-oxoglutarate-dependent nucleic Acid demethylase. J.Med.Chem., 55:2173-2184, 2012 Cited by PubMed Abstract: 2-Oxoglutarate-dependent nucleic acid demethylases are of biological interest because of their roles in nucleic acid repair and modification. Although some of these enzymes are linked to physiology, their regulatory roles are unclear. Hence, there is a desire to develop selective inhibitors for them; we report studies on AlkB, which reveal it as being amenable to selective inhibition by small molecules. Dynamic combinatorial chemistry linked to mass spectrometric analyses (DCMS) led to the identification of lead compounds, one of which was analyzed by crystallography. Subsequent structure-guided studies led to the identification of inhibitors of improved potency, some of which were shown to be selective over two other 2OG oxygenases. The work further validates the use of the DCMS method and will help to enable the development of inhibitors of nucleic acid modifying 2OG oxygenases both for use as functional probes and, in the longer term, for potential therapeutic use. PubMed: 22263962DOI: 10.1021/jm201417e PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.001 Å) |
Structure validation
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