4IDZ
Crystal structure of the human fat mass and obesity associated protein (FTO) in complex with N-oxalylglycine (NOG)
Summary for 4IDZ
| Entry DOI | 10.2210/pdb4idz/pdb |
| Related | 3LFM 4IE0 4IE4 4IE5 4IE6 4IE7 |
| Descriptor | Alpha-ketoglutarate-dependent dioxygenase FTO, N-OXALYLGLYCINE, GLYCEROL, ... (5 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 | Homo sapiens (human) |
| Cellular location | Nucleus : Q9C0B1 |
| Total number of polymer chains | 1 |
| Total formula weight | 57120.92 |
| Authors | Aik, W.S.,McDonough, M.A.,Schofield, C.J. (deposition date: 2012-12-13, release date: 2013-04-03, Last modification date: 2024-11-20) |
| Primary citation | Aik, W.S.,Demetriades, M.,Hamdan, M.K.K.,Bagg, E.A.L.,Yeoh, K.K.,Lejeune, C.,Zhang, Z.,McDonough, M.A.,Schofield, C.J. Structural basis for inhibition of the fat mass and obesity associated protein (FTO) J.Med.Chem., 56:3680-3688, 2013 Cited by PubMed Abstract: The fat mass and obesity associated protein (FTO) is a potential target for anti-obesity medicines. FTO is a 2-oxoglutarate (2OG)-dependent N-methyl nucleic acid demethylase that acts on substrates including 3-methylthymidine, 3-methyluracil, and 6-methyladenine. To identify FTO inhibitors, we screened a set of 2OG analogues and related compounds using differential scanning fluorometry- and liquid chromatography-based assays. The results revealed sets of both cyclic and acyclic 2OG analogues that are FTO inhibitors. Identified inhibitors include small molecules that have been used in clinical studies for the inhibition of other 2OG oxygenases. Crystallographic analyses reveal inhibition by 2OG cosubstrate or primary substrate competitors as well as compounds that bind across both cosubstrate and primary substrate binding sites. The results will aid the development of more potent and selective FTO inhibitors. PubMed: 23547775DOI: 10.1021/jm400193d PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.46 Å) |
Structure validation
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