8AHM
Crystal structure of tubulin in complex with C(13)/C(13')-Bis-Desmethyl-Disorazole Z
Summary for 8AHM
| Entry DOI | 10.2210/pdb8ahm/pdb |
| Descriptor | Tubulin alpha-1B chain, GUANOSINE-5'-DIPHOSPHATE, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, ... (14 entities in total) |
| Functional Keywords | tubulin, inhibitor, complex, cell cycle |
| Biological source | Rattus norvegicus (Norway rat) More |
| Total number of polymer chains | 6 |
| Total formula weight | 270989.85 |
| Authors | Oliva, M.A.,Diaz, J.F.,Altmann, K.H. (deposition date: 2022-07-22, release date: 2022-11-16, Last modification date: 2024-02-07) |
| Primary citation | Bold, C.P.,Lucena-Agell, D.,Oliva, M.A.,Diaz, J.F.,Altmann, K.H. Synthesis and Biological Evaluation of C(13)/C(13')-Bis(desmethyl)disorazole Z. Angew.Chem.Int.Ed.Engl., 62:e202212190-e202212190, 2023 Cited by PubMed Abstract: We describe the total synthesis of the macrodiolide C(13)/C(13')-bis(desmethyl)disorazole Z through double inter-/intramolecular Stille cross-coupling of a monomeric vinyl stannane/vinyl iodide precursor to form the macrocycle. The key step in the synthesis of this precursor was a stereoselective aldol reaction of a formal Evans acetate aldol product with crotonaldehyde. As demonstrated by X-ray crystallography, the binding mode of C(13)/C(13')-bis(desmethyl)disorazole Z to tubulin is virtually identical with that of the natural product disorazole Z. Likewise, C(13)/C(13')-bis(desmethyl)disorazole Z inhibits tubulin assembly with at least the same potency as disorazole Z and it appears to be a more potent cell growth inhibitor. PubMed: 36281761DOI: 10.1002/anie.202212190 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.42 Å) |
Structure validation
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