4IE4: Crystal Structure of the Human FAT Mass and Obesity Associated Protein (Fto) in Complex With 5-carboxy-8-hydroxyquinoline (Iox1)

Citation:
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.
PDB ID: 4IE4Download
MMDB ID: 108883
PDB Deposition Date: 2012/12/13
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 2.5048  Å
Source Organism:
Similar Structures:
Biological Unit for 4IE4: monomeric; determined by author and by software (PISA)
Molecular Components in 4IE4
Label Count Molecule
Protein (1 molecule)
1
Alpha-ketoglutarate-dependent Dioxygenase FTO(Gene symbol: FTO)
Molecule annotation
Chemicals (3 molecules)
1
1
2
1
3
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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