Structural highlights
3ro4 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.
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| Ligands: | , |
| Related: | 3nbv, 3nbw, 3nc2, 3nc9, 3nca |
| 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
A series of indazoles have been discovered as KHK inhibitors from a pyrazole hit identified through fragment-based drug discovery (FBDD). The optimization process guided by both X-ray crystallography and solution activity resulted in lead-like compounds with good pharmaceutical properties.
Optimization of a pyrazole hit from FBDD into a novel series of indazoles as ketohexokinase inhibitors.,Zhang X, Song F, Kuo GH, Xiang A, Gibbs AC, Abad MC, Sun W, Kuo LC, Sui Z Bioorg Med Chem Lett. 2011 Aug 15;21(16):4762-7. Epub 2011 Jun 29. PMID:21767952[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
- ↑ Zhang X, Song F, Kuo GH, Xiang A, Gibbs AC, Abad MC, Sun W, Kuo LC, Sui Z. Optimization of a pyrazole hit from FBDD into a novel series of indazoles as ketohexokinase inhibitors. Bioorg Med Chem Lett. 2011 Aug 15;21(16):4762-7. Epub 2011 Jun 29. PMID:21767952 doi:10.1016/j.bmcl.2011.06.067
