3mar
Crystal structure of homodimeric R132H mutant of human cytosolic NADP(+)-dependent isocitrate dehydrogenase in complex with NADPCrystal structure of homodimeric R132H mutant of human cytosolic NADP(+)-dependent isocitrate dehydrogenase in complex with NADP
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
3mar is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
- ↑ Yang B, Zhong C, Peng Y, Lai Z, Ding J. Molecular mechanisms of "off-on switch" of activities of human IDH1 by tumor-associated mutation R132H. Cell Res. 2010 Nov;20(11):1188-200. Epub 2010 Oct 26. PMID:20975740 doi:10.1038/cr.2010.145