MolNFT v1 · #185203 · protein
Crystal structure of ivosidenib-resistant IDH1 variant R132C S280F in complex with NADPH and inhibitor ds-1001B
7PJN · Isocitrate dehydrogenase [NADP] cytoplasmic: “Crystal structure of ivosidenib-resistant IDH1 variant R132C S280F in complex with NADPH and inhibitor…”. X-ray diffraction, 2 ligands (7SU, NDP), 20 pockets (best druggability 0.88).…
- PDB
- 7PJN
- Type
- protein
- Length
- 1,622 residues
- Chains
- 4
- Method
- x-ray diffraction
- Collection
- MolNFT v1 / PDB
- Contract
- 0xDE3723766Bc32dcACD03C17BaA400A7B36837Eba
- Owner
- 0x3396CDB397284571d12822B4ae1189a8E22AAAAA
- Molecule
- Isocitrate dehydrogenase [NADP] cytoplasmic
- EC
- 1.1.1.42
- UniProt
- O75874
- Ligands
- 7SU, NDP
- Pockets
- 20 · best druggability 0.88
Structure
x-ray diffraction · 4 distinct chains · 46% helix, 22% strand (DSSP).
| Chain | Molecule | Type | Residues | Secondary structure | UniProt |
|---|---|---|---|---|---|
| A | Isocitrate dehydrogenase [NADP] cytoplasmic (EC 1.1.1.42) | protein | 406 | 46% helix, 22% strand | O75874 |
| B | Isocitrate dehydrogenase [NADP] cytoplasmic (EC 1.1.1.42) | protein | 405 | 45% helix, 23% strand | O75874 |
| C | Isocitrate dehydrogenase [NADP] cytoplasmic (EC 1.1.1.42) | protein | 403 | 46% helix, 23% strand | O75874 |
| D | Isocitrate dehydrogenase [NADP] cytoplasmic (EC 1.1.1.42) | protein | 408 | 46% helix, 21% strand | O75874 |
Ligands and binding sites
- 7SU · (E)-3-(1-(5-(2-fluoropropan-2-yl)-3-(2,4,6-trichlorophenyl)isoxazole-4-carbonyl)-3-methyl-1H-indol-4-yl)acrylic acid · ligand · 4 copies · chains A, B, C, D
- NDP · Nadph dihydro-nicotinamide-adenine-dinucleotide phosphate · ligand · 4 copies · chains A, B, C, D
- GOL · Glycerol · additive · 6 copies · chains A, B, C, D
- CIT · Citric acid · additive · 5 copies · chains A, B, C, D
Binding sites are the residues within 4.5 Å of a ligand's heavy atoms.
Pockets
20 pockets found on a 1 Å grid, 9 with a druggability of 0.5 or more.
| Volume (ų) | Druggability | Buriedness | Lining residues | Inside | |
|---|---|---|---|---|---|
| 1 | 928 | 0.88 | 0.89 | 97 | 7SU |
| 2 | 703 | 0.75 | 0.80 | 75 | 7SU, CIT |
| 3 | 333 | 0.72 | 0.84 | 42 | 7SU |
| 4 | 720 | 0.69 | 0.76 | 77 | CIT, NDP |
| 5 | 359 | 0.63 | 0.78 | 35 | NDP |
Interfaces
3 interfaces between chains.
- B–C · 2600 Ų buried · 40 hydrogen bonds · protein-protein
- A–B · 691 Ų buried · 13 hydrogen bonds · protein-protein
- C–D · 336 Ų buried · 5 hydrogen bonds · protein-protein
Modifications
Observed in the structure: 4 disulfide, 1 modified (disulfide, oxidation).
Compared structures
- 7PJN · Crystal Structure of Ivosidenib-resistant IDH1 variant R132C S280F in complex with NADPH… · the same entry in another collection · chain D against D, TM-score 1.00
- O75874 · AlphaFold monomer V2.0 prediction for isocitrate dehydrogenase [NADP] cytoplasmic (O75874) · a predicted model of the same protein · chain A against A, TM-score 0.96
Analyse
- Open in the research workbench: secondary structure, accessibility, pockets, interfaces, conservation, variants, modifications, peptides and crosslinks on the 3D structure
- Every structure of UniProt O75874
- Elsewhere: RCSB PDB 7PJN · PDBe 7PJN · UniProt O75874
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