4QB3
Crystal structure of the first bromodomain of human BRD4 in complex with Olinone
Summary for 4QB3
| Entry DOI | 10.2210/pdb4qb3/pdb |
| Descriptor | Bromodomain-containing protein 4, N-[4-(1-oxo-1,2,3,4-tetrahydro-5H-pyrido[4,3-b]indol-5-yl)butyl]acetamide, 1,2-ETHANEDIOL, ... (4 entities in total) |
| Functional Keywords | bromodomain, transcription factor, acetyl-lysine binding, transcription-transcription inhibitor complex, transcription/transcription inhibitor |
| Biological source | Homo sapiens (human) |
| Cellular location | Nucleus: O60885 |
| Total number of polymer chains | 1 |
| Total formula weight | 15460.82 |
| Authors | Plotnikov, A.N.,Joshua, J.,Zhou, M.-M. (deposition date: 2014-05-06, release date: 2015-04-22, Last modification date: 2023-09-20) |
| Primary citation | Gacias, M.,Gerona-Navarro, G.,Plotnikov, A.N.,Zhang, G.,Zeng, L.,Kaur, J.,Moy, G.,Rusinova, E.,Rodriguez, Y.,Matikainen, B.,Vincek, A.,Joshua, J.,Casaccia, P.,Zhou, M.M. Selective chemical modulation of gene transcription favors oligodendrocyte lineage progression. Chem.Biol., 21:841-854, 2014 Cited by PubMed Abstract: Lysine acetylation regulates gene expression through modulating protein-protein interactions in chromatin. Chemical inhibition of acetyl-lysine binding bromodomains of the major chromatin regulators BET (bromodomain and extraterminal domain) proteins has been shown to effectively block cell proliferation in cancer and inflammation. However, whether selective inhibition of individual BET bromodomains has distinctive functional consequences remains only partially understood. In this study, we show that selective chemical inhibition of the first bromodomain of BET proteins using our small-molecule inhibitor, Olinone, accelerated the progression of mouse primary oligodendrocyte progenitors toward differentiation, whereas inhibition of both bromodomains of BET proteins hindered differentiation. This effect was target specific, as it was not detected in cells treated with inactive analogs and independent of any effect on proliferation. Therefore, selective chemical modulation of individual bromodomains, rather than use of broad-based inhibitors, may enhance regenerative strategies in disorders characterized by myelin loss such as aging and neurodegeneration. PubMed: 24954007DOI: 10.1016/j.chembiol.2014.05.009 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (0.94 Å) |
Structure validation
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