3GG3: Crystal Structure of the Bromodomain of Human PCAF

Citation:
Abstract
Bromodomains (BRDs) are protein interaction modules that specifically recognize epsilon-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.
PDB ID: 3GG3Download
MMDB ID: 70281
PDB Deposition Date: 2009/2/27
Updated in MMDB: 2011/05
Experimental Method:
x-ray diffraction
Resolution: 2.25  Å
Source Organism:
Similar Structures:
Biological Unit for 3GG3: monomeric; determined by author and by software (PISA)
Molecular Components in 3GG3
Label Count Molecule
Protein (1 molecule)
1
Histone Acetyltransferase Pcaf(Gene symbol: KAT2B)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

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