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NADP isocitrate dehydrogenase 2 (isocitrate dehydrogenase [NADP] mitochondrial)
Function:
- catalyzes reversable conversion of isocitrate to 2-oxoglutarate
- role in intermediary metabolism & energy production
- may tightly associate or interact with pyruvate dehydrogenase complex
isocitrate + NADP+ 2-oxoglutarate + CO2 + NADPH
Cofactor:
- binds 1 Mg+2 or Mn+2 per subunit
Structure:
- homodimer
- belongs to the isocitrate & isopropylmalate dehydrogenases family
Compartment: mitochondria
Laboratory:
- IDH2 gene mutation
Pharmacology:
- IDH2 inhibitor enasidenib (Idhifa) FDA-approved for treatment of refactory acute myeloid leukemia (AML) with IDH2 gene mutation
- apparently IDH2 promotes cell growth of AML myelobasts
- vorasidenib (Servier) inhibits mutant IDH2 investigational treatment of gliomas with IDH2 gene mutation
General
metalloprotein
mitochondrial protein
NADP isocitrate dehydrogenase
Properties
SIZE: entity length = 452 aa
MW = 51 kD
COMPARTMENT: mitochondria
MOTIF: cofactor-binding site [115-117]
COFACTOR-BOUND: NADP
MOTIF: binding site
SITE: 117-117
FOR-BINDING-OF: Substrate
cofactor-binding site [122-122]
COFACTOR-BOUND: NADP
Substrate binding {134-140}
binding site
SITE: 149-149
FOR-BINDING-OF: Substrate
binding site
SITE: 172-172
FOR-BINDING-OF: Substrate
tyrosine residue {179}
lysine residue {251}
manganese [Mn]-binding site
SITE: 291-291
cofactor-binding site [299-299]
COFACTOR-BOUND: NADP
manganese [Mn]-binding site
SITE: 314-314
cofactor-binding site [349-354]
COFACTOR-BOUND: NADP
cofactor-binding site [367-367]
COFACTOR-BOUND: NADP
Database Correlations
OMIM 147650
UniProt P48735
Pfam PF00180
Kegg hsa:3418
ENZYME 1.1.1.42
References
- UniProt :accession O75874
- FDA News Release. August 1, 2017
FDA approves new targeted treatment for relapsed or refractory
acute myeloid leukemia.
https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm569421.htm