4l04
Crystal Structure Analysis of human IDH1 mutants in complex with NADP+ and Ca2+/alpha-KetoglutarateCrystal Structure Analysis of human IDH1 mutants in complex with NADP+ and Ca2+/alpha-Ketoglutarate
Template:ABSTRACT PUBMED 23731180
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
4l04 is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
- ↑ Rendina AR, Pietrak B, Smallwood A, Zhao H, Qi H, Quinn C, Adams ND, Concha N, Duraiswami C, Thrall SH, Sweitzer S, Schwartz B. Mutant IDH1 Enhances the Production of 2-Hydroxyglutarate Due to Its Kinetic Mechanism. Biochemistry. 2013 Jul 2;52(26):4563-77. doi: 10.1021/bi400514k. Epub 2013 Jun, 21. PMID:23731180 doi:10.1021/bi400514k