4i3k

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Template:STRUCTURE 4i3k

Crystal structure of a metabolic reductase with 1-hydroxy-6-(4-hydroxybenzyl)-4-methylpyridin-2(1H)-oneCrystal structure of a metabolic reductase with 1-hydroxy-6-(4-hydroxybenzyl)-4-methylpyridin-2(1H)-one

Template:ABSTRACT PUBMED 23795241

DiseaseDisease

[IDHC_HUMAN] Defects in IDH1 are involved in the development of glioma (GLM) [MIM:137800]. Gliomas are central nervous system neoplasms derived from glial cells and comprise astrocytomas, glioblastoma multiforme, oligodendrogliomas, and ependymomas. Note=Mutations affecting Arg-132 are tissue-specific, and suggest that this residue plays a unique role in the development of high-grade gliomas. Mutations of Arg-132 to Cys, His, Leu or Ser abolish magnesium binding and abolish the conversion of isocitrate to alpha-ketoglutarate. Instead, alpha-ketoglutarate is converted to R(-)-2-hydroxyglutarate. Elevated levels of R(-)-2-hydroxyglutarate are correlated with an elevated risk of malignant brain tumors.

About this StructureAbout this Structure

4i3k is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

[xtra 1]

  1. Zheng B, Yao Y, Liu Z, Deng L, Anglin JL, Jiang H, Prasad BV, Song Y. Crystallographic Investigation and Selective Inhibition of Mutant Isocitrate Dehydrogenase. ACS Med Chem Lett. 2013 Jun 13;4(6):542-546. PMID:23795241 doi:10.1021/ml400036z

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