8QH9
X-ray structure of Danio rerio histone deacetylase 6 (HDAC6) CD2 in complex with a S-29b
Summary for 8QH9
| Entry DOI | 10.2210/pdb8qh9/pdb |
| Descriptor | Histone deacetylase 6, ZINC ION, POTASSIUM ION, ... (8 entities in total) |
| Functional Keywords | protein deacetylase, histone deacetylase 6, zinc binding group, inhibitor, danio rerio, hydrolase |
| Biological source | Danio rerio (zebrafish) |
| Total number of polymer chains | 1 |
| Total formula weight | 40874.68 |
| Authors | |
| Primary citation | Scheuerer, S.,Motlova, L.,Schaker-Hubner, L.,Sellmer, A.,Feller, F.,Ertl, F.J.,Koch, P.,Hansen, F.K.,Barinka, C.,Mahboobi, S. Biological and structural investigation of tetrahydro-beta-carboline-based selective HDAC6 inhibitors with improved stability. Eur.J.Med.Chem., 276:116676-116676, 2024 Cited by PubMed Abstract: Our previously reported HDAC6 inhibitor (HDAC6i) Marbostat-100 (4) has provided many arguments for further clinical evaluation. By the substitution of the acidic hydrogen of 4 for different carbon residues, we were able to generate an all-carbon stereocenter, which significantly improves the hydrolytic stability of the inhibitor. Further asymmetric synthesis has shown that the (S)-configured inhibitors preferentially bind to HDAC6. This led to the highly selective and potent methyl-substituted derivative S-29b, which elicited a long-lasting tubulin hyperacetylation in MV4-11 cells. Finally, a crystal structure of the HDAC6/S-29b complex provided mechanistic explanation for the high potency and stereoselectivity of synthesized compound series. PubMed: 39067437DOI: 10.1016/j.ejmech.2024.116676 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.59 Å) |
Structure validation
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