› 6bl0

X-ray diffraction
2.17Å resolution

Novel Modes of Inhibition of Wild-Type IDH1:Direct Covalent Modification of His315 with Cmpd11

Released:
DOI: 10.2210/pdb6bl0/pdb
PDB entry 6bl0 coloured by chain, front view.
PDB entry 6bl0 coloured by chain, side view.
PDB entry 6bl0 coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Novel Modes of Inhibition of Wild-Type Isocitrate Dehydrogenase 1 (IDH1): Direct Covalent Modification of His315.
Jakob CG, Upadhyay AK, Donner PL, Nicholl E, Addo SN, Qiu W, Ling C, Gopalakrishnan SM, Torrent M, Cepa SP, Shanley J, Shoemaker AR, Sun CC, Vasudevan A, Woller KR, Shotwell JB, Shaw B, Bian Z, Hutti JE
J Med Chem 61 6647-6657 (2018)
PMID: 30004704

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: 425 amino acids
Theoretical weight: 48.15 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 2 x NAP
3 bound ligands:
Ligand MG 3 x MG
Ligand ICT 3 x ICT
Ligand DWJ 1 x DWJ
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 17-ID
Spacegroup: C2221
Unit cell:
a: 98.195Å b: 274.328Å c: 115.059Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.197 0.196 0.227
Expression system: Escherichia coli

Quick links

Citations

5 review citations

Recent Advances in Selective and Irreversible Covalent Ligand Development and Validation.
Zhang et al. (2019)
4 more

1 mention without citation

Water Networks and Correlated Motions in Mutant Isocitrate Dehydrogenase 1 (IDH1) Are Critical for Allosteric Inhibitor Binding and Activity.
Chambers et al. (2020)