5MGM
Crystal Structure of BAZ2A bromodomain in complex with acetophenone derivative 4
Summary for 5MGM
| Entry DOI | 10.2210/pdb5mgm/pdb |
| Related | 5MGJ 5MGK 5MGL |
| Descriptor | Bromodomain adjacent to zinc finger domain protein 2A, 1-(3-pyrimidin-2-yloxyphenyl)ethanone (3 entities in total) |
| Functional Keywords | four helical bundle, transcription |
| Biological source | Homo sapiens (Human) |
| Cellular location | Nucleus, nucleolus : Q9UIF9 |
| Total number of polymer chains | 1 |
| Total formula weight | 12595.14 |
| Authors | Lolli, G.,Spiliotopoulos, D.,Caflisch, A. (deposition date: 2016-11-21, release date: 2017-04-12, Last modification date: 2024-01-17) |
| Primary citation | Spiliotopoulos, D.,Wamhoff, E.C.,Lolli, G.,Rademacher, C.,Caflisch, A. Discovery of BAZ2A bromodomain ligands. Eur J Med Chem, 139:564-572, 2017 Cited by PubMed Abstract: The bromodomain adjacent to zinc finger domain protein 2A (BAZ2A) is implicated in aggressive prostate cancer. The BAZ2A bromodomain is a challenging target because of the shallow pocket of its natural ligand, the acetylated side chain of lysine. Here, we report the successful screening of a library of nearly 1500 small molecules by high-throughput docking and force field-based binding-energy evaluation. For seven of the 20 molecules selected in silico, evidence of binding to the BAZ2A bromodomain is provided by ligand-observed NMR spectroscopy. Two of these compounds show a favorable ligand efficiency of 0.42 kcal/mol per non-hydrogen atom in a competition-binding assay. The crystal structures of the BAZ2A bromodomain in complex with four fragment hits validate the predicted binding modes. The binding modes of compounds 1 and 3 are compatible with ligand growing for optimization of affinity for BAZ2A and selectivity against the close homologue BAZ2B. PubMed: 28837921DOI: 10.1016/j.ejmech.2017.08.028 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.8 Å) |
Structure validation
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