| Structural highlights
3q92 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , |
| Related: | 3nc9, 3nbv, 3nbw, 3nc2, 3nca, 3qa2, 3qai |
| Gene: | KHK (HUMAN) |
| Activity: | Ketohexokinase, with EC number 2.7.1.3 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Disease
[KHK_HUMAN] Defects in KHK are the cause of fructosuria (FRUCT) [MIM:229800]. Benign defect of intermediary metabolism.[1] [2]
Publication Abstract from PubMed
Attenuation of fructose metabolism by the inhibition of ketohexokinase (KHK; fructokinase) should reduce body weight, free fatty acids, and triglycerides, thereby offering a novel approach to treat diabetes and obesity in response to modern diets. We have identified potent, selective inhibitors of human hepatic KHK within a series of pyrimidinopyrimidines (1). For example, 8, 38, and 47 exhibited KHK IC50 values of 12, 7, and 8 nM, respectively, and also showed potent cellular KHK inhibition (IC50 < 500 nM), which relates to their intrinsic potency vs KHK and their ability to penetrate cells. X-ray cocrystal structures of KHK complexes of 3, 8, and 47 revealed the important interactions within the enzyme's adenosine 5'-triphosphate (ATP)-binding pocket.
Inhibitors of Ketohexokinase: Discovery of Pyrimidinopyrimidines with Specific Substitution that Complements the ATP-Binding Site.,Maryanoff BE, O'Neill JC, McComsey DF, Yabut SC, Luci DK, Jordan AD Jr, Masucci JA, Jones WJ, Abad MC, Gibbs AC, Petrounia I ACS Med Chem Lett. 2011 Apr 18;2(7):538-43. doi: 10.1021/ml200070g. eCollection, 2011 Jul 14. PMID:24900346[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Trinh CH, Asipu A, Bonthron DT, Phillips SE. Structures of alternatively spliced isoforms of human ketohexokinase. Acta Crystallogr D Biol Crystallogr. 2009 Mar;65(Pt 3):201-11. Epub 2009, Feb 20. PMID:19237742 doi:S0907444908041115
- ↑ Bonthron DT, Brady N, Donaldson IA, Steinmann B. Molecular basis of essential fructosuria: molecular cloning and mutational analysis of human ketohexokinase (fructokinase). Hum Mol Genet. 1994 Sep;3(9):1627-31. PMID:7833921
- ↑ Maryanoff BE, O'Neill JC, McComsey DF, Yabut SC, Luci DK, Jordan AD Jr, Masucci JA, Jones WJ, Abad MC, Gibbs AC, Petrounia I. Inhibitors of Ketohexokinase: Discovery of Pyrimidinopyrimidines with Specific Substitution that Complements the ATP-Binding Site. ACS Med Chem Lett. 2011 Apr 18;2(7):538-43. doi: 10.1021/ml200070g. eCollection, 2011 Jul 14. PMID:24900346 doi:http://dx.doi.org/10.1021/ml200070g
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