› 5i95

X-ray diffraction
1.54Å resolution

Crystal Structure of Human Mitochondrial Isocitrate Dehydrogenase R140Q Mutant Homodimer bound to NADPH and alpha-Ketoglutaric acid

Released:
DOI: 10.2210/pdb5i95/pdb
PDB entry 5i95 coloured by chain, front view.
PDB entry 5i95 coloured by chain, side view.
PDB entry 5i95 coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
AG-221, a First-in-Class Therapy Targeting Acute Myeloid Leukemia Harboring Oncogenic IDH2 Mutations.
Yen K, Travins J, Wang F, David MD, Artin E, Straley K, Padyana A, Gross S, DeLaBarre B, Tobin E, Chen Y, Nagaraja R, Choe S, Jin L, Konteatis Z, Cianchetta G, Saunders JO, Salituro FG, Quivoron C, Opolon P, Bawa O, Saada V, Paci A, Broutin S, Bernard OA, de Botton S, Marteyn BS, Pilichowska M, Xu Y, Fang C, Jiang F, Wei W, Jin S, Silverman L, Liu W, Yang H, Dang L, Dorsch M, Penard-Lacronique V, Biller SA, Su SM
Cancer Discov 7 478-493 (2017)
PMID: 28193778

Function and Biology Details

Reaction catalysed: 
(1a) isocitrate + NADP(+) = 2-oxalosuccinate + NADPH
Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
homo dimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-155800 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Isocitrate dehydrogenase [NADP], mitochondrial Chain: A
Molecule details ›
Chain: A
Length: 424 amino acids
Theoretical weight: 48.13 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: P48735 (Residues: 39-452; Coverage: 92%)
Gene name: IDH2
Sequence domains: Isocitrate/isopropylmalate dehydrogenase
Structure domains: Isopropylmalate Dehydrogenase

Ligands and Environments


Cofactor: Ligand NDP 1 x NDP
4 bound ligands:
Ligand CA 1 x CA
Ligand GOL 4 x GOL
Ligand ACT 1 x ACT
Ligand AKG 1 x AKG
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SSRF BEAMLINE BL17U
Spacegroup: C2221
Unit cell:
a: 67.178Å b: 154.875Å c: 93.57Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.144 0.142 0.174
Expression system: Escherichia coli BL21(DE3)

Quick links

Citations

119 review citations

The impact of cellular metabolism on chromatin dynamics and epigenetics.
Reid et al. (2017)
118 more

4 mentions without citation

Isocitrate dehydrogenase variants in cancer - Cellular consequences and therapeutic opportunities.
Liu et al. (2020)
3 more