9B81
Crystal structure of wild type IDH1 bound to compound 4
This is a non-PDB format compatible entry.
Summary for 9B81
| Entry DOI | 10.2210/pdb9b81/pdb |
| Descriptor | Isocitrate dehydrogenase [NADP] cytoplasmic, 2-methyl-2-(6-{4-[(2S)-1,1,1-trifluoro-2-hydroxypropan-2-yl]benzoyl}-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepin-8-yl)propanenitrile, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, ... (5 entities in total) |
| Functional Keywords | oxidoreductase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 2 |
| Total formula weight | 98637.08 |
| Authors | Lu, J.,Abeywickrema, P.,Heo, M.R.,Parthasarathy, G.,McCoy, M.,Soisson, S.M. (deposition date: 2024-03-28, release date: 2025-03-26) |
| Primary citation | McCoy, M.A.,Lu, J.,Richard Miller, F.,Soisson, S.M.,Lam, M.H.,Fischer, C. Biostructural, biochemical and biophysical studies of mutant IDH1. Nat Commun, 15:7877-7877, 2024 Cited by PubMed Abstract: We report bio-structural, bio-chemical and bio-physical evidence demonstrating how small molecules can bind to both wild-type and mutant IDH1, but only inhibit the enzymatic activity of the mutant isoform. Enabled through x-ray crystallography, we characterized a series of small molecule inhibitors that bound to mutant IDH1 differently than the marketed inhibitor Ivosidenib, for which we have determined the x-ray crystal structure. Across the industry several mutant IDH1 inhibitor chemotypes bind to this allosteric IDH1 pocket and selectively inhibit the mutant enzyme. Detailed characterization by a variety of biophysical techniques and NMR studies led us to propose how compounds binding in the allosteric IDH1 R132H pocket inhibit the production of 2-Hydroxy glutarate. PubMed: 39251618DOI: 10.1038/s41467-024-51692-0 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.56 Å) |
Structure validation
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