2YEK
Crystal Structure of the First Bromodomain of Human Brd2 with the inhibitor GSK525762 (IBET)
Summary for 2YEK
| Entry DOI | 10.2210/pdb2yek/pdb |
| Related | 1X0J 2YDW 2YEL 2YEM |
| Descriptor | BROMODOMAIN-CONTAINING PROTEIN 2, 2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide, SULFATE ION, ... (4 entities in total) |
| Functional Keywords | signaling protein, histone, epigenetic reader |
| Biological source | HOMO SAPIENS |
| Cellular location | Nucleus (Probable): P25440 |
| Total number of polymer chains | 3 |
| Total formula weight | 54706.39 |
| Authors | Chung, C.W. (deposition date: 2011-03-25, release date: 2011-06-15, Last modification date: 2024-05-08) |
| Primary citation | Chung, C.W.,Coste, H.,White, J.H.,Mirguet, O.,Wilde, J.,Gosmini, R.L.,Delves, C.,Magny, S.M.,Woodward, R.,Hughes, S.A.,Boursier, E.V.,Flynn, H.,Bouillot, A.M.,Bamborough, P.,Brusq, J.M.,Gellibert, F.J.,Jones, E.J.,Riou, A.M.,Homes, P.,Martin, S.L.,Uings, I.J.,Toum, J.,Clement, C.A.,Boullay, A.B.,Grimley, R.L.,Blandel, F.M.,Prinjha, R.K.,Lee, K.,Kirilovsky, J.,Nicodeme, E. Discovery and Characterization of Small Molecule Inhibitors of the Bet Family Bromodomains. J.Med.Chem., 54:3827-, 2011 Cited by PubMed Abstract: Epigenetic mechanisms of gene regulation have a profound role in normal development and disease processes. An integral part of this mechanism occurs through lysine acetylation of histone tails which are recognized by bromodomains. While the biological and structural characterization of many bromodomain containing proteins has advanced considerably, the therapeutic tractability of this protein family is only now becoming understood. This paper describes the discovery and molecular characterization of potent (nM) small molecule inhibitors that disrupt the function of the BET family of bromodomains (Brd2, Brd3, and Brd4). By using a combination of phenotypic screening, chemoproteomics, and biophysical studies, we have discovered that the protein-protein interactions between bromodomains and acetylated histones can be antagonized by selective small molecules that bind at the acetylated lysine recognition pocket. X-ray crystal structures of compounds bound into bromodomains of Brd2 and Brd4 elucidate the molecular interactions of binding and explain the precisely defined stereochemistry required for activity. PubMed: 21568322DOI: 10.1021/JM200108T PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.98 Å) |
Structure validation
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