› 6vei

X-ray diffraction
2.1Å resolution

Crystal Structure of Human Cytosolic Isocitrate Dehydrogenase (IDH1) R132H Mutant in Complex with NADPH and AG-881 (Vorasidenib) Inhibitor

Released:
DOI: 10.2210/pdb6vei/pdb
PDB entry 6vei coloured by chain, front view.
PDB entry 6vei coloured by chain, side view.
PDB entry 6vei coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Vorasidenib (AG-881): A First-in-Class, Brain-Penetrant Dual Inhibitor of Mutant IDH1 and 2 for Treatment of Glioma.
Konteatis Z, Artin E, Nicolay B, Straley K, Padyana AK, Jin L, Chen Y, Narayaraswamy R, Tong S, Wang F, Zhou D, Cui D, Cai Z, Luo Z, Fang C, Tang H, Lv X, Nagaraja R, Yang H, Su SM, Sui Z, Dang L, Yen K, Popovici-Muller J, Codega P, Campos C, Mellinghoff IK, Biller SA
ACS Med Chem Lett 11 101-107 (2020)
PMID: 32071674

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-131150 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Isocitrate dehydrogenase [NADP] cytoplasmic Chains: A, B
Molecule details ›
Chains: A, B
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

Ligands and Environments


Cofactor: Ligand NDP 2 x NDP
7 bound ligands:
Ligand SO4 1 x SO4
Ligand 33O 1 x 33O
Ligand PEG 4 x PEG
Ligand ACT 1 x ACT
Ligand MLA 1 x MLA
Ligand 9UO 1 x 9UO
Ligand MLT 1 x MLT
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SSRF BEAMLINE BL17B1
Spacegroup: P21212
Unit cell:
a: 117.213Å b: 85.099Å c: 96.663Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.159 0.158 0.195
Expression system: Escherichia coli

Quick links

Citations

39 review citations

Mechanisms of Metabolic Reprogramming in Cancer Cells Supporting Enhanced Growth and Proliferation.
Schiliro et al. (2021)
38 more

3 mentions without citation

Mutated Isocitrate Dehydrogenase (mIDH) as Target for PET Imaging in Gliomas.
Neumaier et al. (2023)
2 more