› 7pjm

X-ray diffraction
2.1Å resolution

Crystal Structure of Ivosidenib-resistant IDH1 variant R132C S280F in complex with NADPH and Ca2+/2-Oxoglutarate

Released:
DOI: 10.2210/pdb7pjm/pdb
PDB entry 7pjm coloured by chain, front view.
PDB entry 7pjm coloured by chain, side view.
PDB entry 7pjm coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Resistance to the isocitrate dehydrogenase 1 mutant inhibitor ivosidenib can be overcome by alternative dimer-interface binding inhibitors.
Reinbold R, Hvinden IC, Rabe P, Herold RA, Finch A, Wood J, Morgan M, Staudt M, Clifton IJ, Armstrong FA, McCullagh JSO, Redmond J, Bardella C, Abboud MI, Schofield CJ
Nat Commun 13 4785 (2022)
PMID: 35970853

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, C
Molecule details ›
Chains: A, B, C
Length: 422 amino acids
Theoretical weight: 47.8 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: O75874 (Residues: 1-414; Coverage: 100%)
Gene names: IDH1, PICD
Sequence domains: Isocitrate/isopropylmalate dehydrogenase

Ligands and Environments


Cofactor: Ligand NDP 3 x NDP
4 bound ligands:
Ligand AKG 3 x AKG
Ligand GOL 4 x GOL
Ligand CA 3 x CA
Ligand CL 3 x CL
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: DIAMOND BEAMLINE I24
Spacegroup: C2221
Unit cell:
a: 96.58Å b: 273.01Å c: 117.42Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.182 0.18 0.21
Expression system: Escherichia coli BL21(DE3)

Quick links

Citations

6 review citations

From Protein Film Electrochemistry to Nanoconfined Enzyme Cascades and the Electrochemical Leaf.
Armstrong et al. (2023)
5 more

2 mentions without citation

Resistance to the isocitrate dehydrogenase 1 mutant inhibitor ivosidenib can be overcome by alternative dimer-interface binding inhibitors.
Reinbold et al. (2022)
1 more