Sandbox Reserved 654: Difference between revisions

The mechanism of protein-protein interaction for the bromodomain of PCAF with histone proteins begins with the acetylation of lysine residues on the histone tail. The acetylation causes a conformational change in the histones. The bromodomains of PCAF and CBP have three major points of contact that allow for site-specific histone recognition.  First, the acetylated lysine of the target protein enters a hydrophobic pocket embedded between the ZA and BC loops at the bottom of the protein.  The Asn803 residue in the bromodomain forms a hydrogen bond with the amide nitrogen of the acetyl-lysine. Next, residues in the ZA and/or BC loops interact with residues adjacent to the acetyl-lysine, which reinforces the acetyl-lysine binding in the bromodomain.  Finally, additional residues in the ZA and BC loops that face opposite to the bromodomain form hydrophobic and/ or electrostatic interaction with the target protein 3 residues away from the acetyl-lysine.  This residue clamps on the BC loop together with the acetyl-lysine side chain that is bound inside the hydrophobic pocket of the bromodomain.[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3339198/]