› 5lge

X-ray diffraction
2.7Å resolution

Crystal Structure of human IDH1 mutant (R132H) in complex with NADP+ and an Inhibitor related to BAY 1436032

Released:
DOI: 10.2210/pdb5lge/pdb
PDB 5lge coloured by chain and viewed from the front.
PDB 5lge coloured by chain and viewed from the side.
PDB 5lge coloured by chain and viewed from the top.
Source organism: Homo sapiens
Primary publication:
Pan-mutant IDH1 inhibitor BAY 1436032 for effective treatment of IDH1 mutant astrocytoma in vivo.
Pusch S, Krausert S, Fischer V, Balss J, Ott M, Schrimpf D, Capper D, Sahm F, Eisel J, Beck AC, Jugold M, Eichwald V, Kaulfuss S, Panknin O, Rehwinkel H, Zimmermann K, Hillig RC, Guenther J, Toschi L, Neuhaus R, Haegebart A, Hess-Stumpp H, Bauser M, Wick W, Unterberg A, Herold-Mende C, Platten M, von Deimling A
Acta Neuropathol. (2017)
PMID: 28124097

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)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Isocitrate dehydrogenase [NADP] cytoplasmic Chains: A, B, C, D
Molecule details ›
Chains: A, B, C, D
Length: 425 amino acids
Theoretical weight: 48.14 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: O75874 (Residues: 1-414; Coverage: 100%)
Gene names: IDH1, PICD
Sequence domains: Isocitrate/isopropylmalate dehydrogenase
Structure domains: Isopropylmalate Dehydrogenase

Ligands and Environments


Cofactor: Ligand NAP 4 x NAP
3 bound ligands:
Ligand EDO 3 x EDO
Ligand 6VN 2 x 6VN
Ligand ACT 1 x ACT
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ESRF BEAMLINE ID29
Spacegroup: C2
Unit cell:
a: 96.9Å b: 110.32Å c: 198.54Å
α: 90° β: 91.19° γ: 90°
R-values:
R R work R free
0.197 0.195 0.23
Expression system: Escherichia coli

Quick links

Citations

39 review citations

Changing paradigms in oncology: Toward noncytotoxic treatments for advanced gliomas.
von Knebel Doeberitz et al. (2022)
38 more

5 mentions without citation

Recent advances of IDH1 mutant inhibitor in cancer therapy.
Tian et al. (2022)
4 more