5DFC
Crystal structure of BRD2(BD2) W370F mutant with ligand I-BET 762 bound
Summary for 5DFC
| Entry DOI | 10.2210/pdb5dfc/pdb |
| Descriptor | Bromodomain-containing protein 2, GLYCEROL, NONAETHYLENE GLYCOL, ... (6 entities in total) |
| Functional Keywords | transcription factors, bet bromodomains, protein mutation engineering, molecular probes, transcription |
| Biological source | Homo sapiens (Human) |
| Cellular location | Nucleus : P25440 |
| Total number of polymer chains | 1 |
| Total formula weight | 14325.54 |
| Authors | Tallant, C.,Baud, M.,Lin-Shiao, E.,Chirgadze, D.Y.,Ciulli, A. (deposition date: 2015-08-26, release date: 2015-11-11, Last modification date: 2024-01-10) |
| Primary citation | Baud, M.G.,Lin-Shiao, E.,Zengerle, M.,Tallant, C.,Ciulli, A. New Synthetic Routes to Triazolo-benzodiazepine Analogues: Expanding the Scope of the Bump-and-Hole Approach for Selective Bromo and Extra-Terminal (BET) Bromodomain Inhibition. J.Med.Chem., 59:1492-1500, 2016 Cited by PubMed Abstract: We describe new synthetic routes developed toward a range of substituted analogues of bromo and extra-terminal (BET) bromodomain inhibitors I-BET762/JQ1 based on the triazolo-benzodiazepine scaffold. These new routes allow for the derivatization of the methoxyphenyl and chlorophenyl rings, in addition to the diazepine ternary center and the side chain methylene moiety. Substitution at the level of the side chain methylene afforded compounds targeting specifically and potently engineered BET bromodomains designed as part of a bump and hole approach. We further demonstrate that marked selectivity for the second over the first bromodomain can be achieved with an indole derivative that exploits differential interaction with an aspartate/histidine conservative substitution on the BC loop of BET bromodomains. PubMed: 26367539DOI: 10.1021/acs.jmedchem.5b01135 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.5 Å) |
Structure validation
Download full validation report
