Sandbox Reserved 654: Difference between revisions

== '''Mechanism''' ==

[[Image:F1.medium.gif |thumb|250 px|right| Acetylation of the lysine and its effects on chromatin remodeling..]]

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, which allows for transcriptional machinery to access DNA. The bromodomains of PCAF within a pretranscriptional initiation complex (PIC) bind to the acetyl-lysine of the histone to stabilize the complex so that transcription may begin. The bromodomains of PCAF have three major points of contact that allow for site-specific histone recognition.  First, the <scene name='Sandbox_Reserved_654/Kac50/1'>acetylated lysine</scene> 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/]