3MB4

Crystal Structure of the fifth Bromodomain of Human Poly-bromodomain containing protein 1 (PB1) with NMP

Summary for 3MB4

• Entry DOI: 10.2210/pdb3mb4/pdb
• Related: 3MB3
• Descriptor: Protein polybromo-1, 1,2-ETHANEDIOL, 1-methylpyrrolidin-2-one, ... (5 entities in total)
• Functional Keywords: pb1, polybromo 1 isoform 1, baf180, polybromo-1d, pbrm1, brg1-associated factor 180, structural genomics consortium, sgc, bromodomain, chromatin regulator, dna-binding, nucleus, phosphoprotein, transcription, transcription regulation
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: Q86U86
• Total number of polymer chains: 2
• Total formula weight: 29946.41

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

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: 22464331
DOI: 10.1016/j.cell.2012.02.013

Experimental method

X-RAY DIFFRACTION (1.66 Å)