2D82
Target Structure-Based Discovery of Small Molecules that Block Human p53 and CREB Binding Protein (CBP) Association
Summary for 2D82
| Entry DOI | 10.2210/pdb2d82/pdb |
| Related | 1jsp |
| NMR Information | BMRB: 6960 |
| Descriptor | CREB-binding protein, 9-ACETYL-2,3,4,9-TETRAHYDRO-1H-CARBAZOL-1-ONE (2 entities in total) |
| Functional Keywords | bromodomain, creb, cbp, p53, chemical ligand, 9-acetyl-2, 3, 4, 9-tetrahydro-carbazol-1-one, transferase |
| Biological source | Homo sapiens (human) |
| Cellular location | Cytoplasm: Q92793 |
| Total number of polymer chains | 1 |
| Total formula weight | 14645.81 |
| Authors | Sachchidanand,Resnick-Silverman, L.,Yan, S.,Mujtaba, S.,Liu, W.J.,Zeng, L.,Manfredi, J.J.,Zhou, M.M. (deposition date: 2005-12-01, release date: 2006-04-04, Last modification date: 2024-05-29) |
| Primary citation | Sachchidanand,Resnick-Silverman, L.,Yan, S.,Mutjaba, S.,Liu, W.J.,Zeng, L.,Manfredi, J.J.,Zhou, M.M. Target structure-based discovery of small molecules that block human p53 and CREB binding protein association Chem.Biol., 13:81-90, 2006 Cited by PubMed Abstract: Lysine acetylation of human tumor suppressor p53 in response to cellular stress signals is required for its function as a transcription factor that regulates cell cycle arrest, senescence, or apoptosis. Here, we report small molecules that block lysine 382-acetylated p53 association with the bromodomain of the coactivator CBP, an interaction essential for p53-induced transcription of the cell cycle inhibitor p21 in response to DNA damage. These chemicals were discovered in target structure-guided nuclear magnetic resonance spectroscopy screening of a focused chemical library constructed based on the structural knowledge of CBP bromodomain/p53-AcK382 binding. Structural characterization shows that these chemicals inhibit CBP/p53 association by binding to the acetyl-lysine binding site of the bromodomain. Cell-based functional assays demonstrate that the lead chemicals can modulate p53 stability and function in response to DNA damage. PubMed: 16426974DOI: 10.1016/j.chembiol.2005.10.014 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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