3MB3
Crystal Structure of the second bromodomain of Pleckstrin homology domain interacting protein (PHIP)
Summary for 3MB3
| Entry DOI | 10.2210/pdb3mb3/pdb |
| Related | 3MB4 |
| Descriptor | PH-interacting protein, 1-methylpyrrolidin-2-one (3 entities in total) |
| Functional Keywords | phip, pleckstrin homology domain interacting protein, dcaf14, ndrp, ddb1 and cul4 associated factor 14, sgc, structural genomics consortium, bromodomain, phosphoprotein, wd repeat, signaling protein |
| Biological source | Homo sapiens (human) |
| Cellular location | Nucleus (By similarity): Q8WWQ0 |
| Total number of polymer chains | 1 |
| Total formula weight | 16230.39 |
| Authors | Filippakopoulos, P.,Picaud, S.,Keates, T.,Ugochukwu, E.,von Delft, F.,Arrowsmith, C.H.,Edwards, A.M.,Weigelt, J.,Bountra, C.,Knapp, S.,Structural Genomics Consortium (SGC) (deposition date: 2010-03-25, release date: 2010-04-14, Last modification date: 2023-09-06) |
| Primary citation | Filippakopoulos, P.,Picaud, S.,Mangos, M.,Keates, T.,Lambert, J.P.,Barsyte-Lovejoy, D.,Felletar, I.,Volkmer, R.,Muller, S.,Pawson, T.,Gingras, A.C.,Arrowsmith, C.H.,Knapp, S. Histone recognition and large-scale structural analysis of the human bromodomain family. Cell(Cambridge,Mass.), 149:214-231, 2012 Cited by PubMed Abstract: Bromodomains (BRDs) are protein interaction modules that specifically recognize ε-N-lysine acetylation motifs, a key event in the reading process of epigenetic marks. The 61 BRDs in the human genome cluster into eight families based on structure/sequence similarity. Here, we present 29 high-resolution crystal structures, covering all BRD families. Comprehensive crossfamily structural analysis identifies conserved and family-specific structural features that are necessary for specific acetylation-dependent substrate recognition. Screening of more than 30 representative BRDs against systematic histone-peptide arrays identifies new BRD substrates and reveals a strong influence of flanking posttranslational modifications, such as acetylation and phosphorylation, suggesting that BRDs recognize combinations of marks rather than singly acetylated sequences. We further uncovered a structural mechanism for the simultaneous binding and recognition of diverse diacetyl-containing peptides by BRD4. These data provide a foundation for structure-based drug design of specific inhibitors for this emerging target family. PubMed: 22464331DOI: 10.1016/j.cell.2012.02.013 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.25 Å) |
Structure validation
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