› 5i96

X-ray diffraction
1.55Å resolution

Crystal Structure of Human Mitochondrial Isocitrate Dehydrogenase (IDH2) R140Q Mutant Homodimer in Complex with AG-221 (Enasidenib) Inhibitor.

Released:
DOI: 10.2210/pdb5i96/pdb
PDB entry 5i96 coloured by chain, front view.
PDB entry 5i96 coloured by chain, side view.
PDB entry 5i96 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 Chains: A, B
Molecule details ›
Chains: A, B
Length: 458 amino acids
Theoretical weight: 51.78 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: P48735 (Residues: 1-452; Coverage: 100%)
Gene name: IDH2
Sequence domains: Isocitrate/isopropylmalate dehydrogenase
Structure domains: Isopropylmalate Dehydrogenase

Ligands and Environments


Cofactor: Ligand NDP 2 x NDP
5 bound ligands:
Ligand CA 2 x CA
Ligand GOL 5 x GOL
Ligand NA 2 x NA
Ligand ACT 2 x ACT
Ligand 69Q 1 x 69Q
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SSRF BEAMLINE BL17U
Spacegroup: P212121
Unit cell:
a: 58.368Å b: 120.348Å c: 124.734Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.165 0.163 0.199
Expression system: Spodoptera frugiperda

Quick links

Citations

119 review citations

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Reid et al. (2017)
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7 mentions without citation

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Westbrook et al. (2020)
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