Sandbox Reserved 654: Difference between revisions

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~~The~~ hydrophobic pocket formed by the loops is the primary binding site for acetyl-lysine proteins. This interaction has been shown via localization and chemical shift experiments that revealed the specific manner with which the bromodomain hydrophobic cavity binds to acetylated lysine residues. Once the acetyl-lysine residue makes the initial binding inside the hydrophobic pocket, the ZA and BC loop residues at the entrance of the pocket interact with the amino acids adjacent (+/- 1 or 2) to the already bound acetyl-lysine. Those interactions reinforce binding of the target sequence. Mujtaba, S. et al (2007) Oncogene 26, 5521. Small structural changes in the conformation of the ZA and BC loops result in exposing other residues that are originally buried within the protein to aid in peptide recognition. Mujtaba, S. et al (2002) Mol. Cell 9, 575.

Until recently, the function of the bromodomain remained unknown. Its structure and modularity, along with its feature of both N and C termini located together on one end of the protein, suggested that it played a role in protein-protein interactions. It has now been shown that the hydrophobic pocket formed by the loops is the primary binding site for acetyl-lysine proteins, making the bromodomain a functional site for recognition of acetylated lysine residues playing a role in regulation via protein-protein interactions. '''Dhalluin'''. This interaction has been shown via localization and chemical shift experiments that revealed the specific manner with which the bromodomain hydrophobic cavity binds to acetylated lysine residues.

Once the acetyl-lysine residue makes the initial binding inside the hydrophobic pocket, the ZA and BC loop residues at the entrance of the pocket interact with the amino acids adjacent (+/- 1 or 2) to the already bound acetyl-lysine. Those interactions reinforce binding of the target sequence. Mujtaba, S. et al (2007) Oncogene 26, 5521. Small structural changes in the conformation of the ZA and BC loops result in exposing other residues that are originally buried within the protein to aid in peptide recognition. Mujtaba, S. et al (2002) Mol. Cell 9, 575.

It is also believed that the bromodomain may also play a role in highly specific histone acetylation by tethering transcriptional HATs to specific chromosomal sites, Brownell, J. et al (1996) Curr. Opin. Genet. Dev. 6, 176, as well as the assembly of multiprotein complexes in transcriptional activation such as the Bromodomain–HIV-1 Tat complex necessary for HIV-1 transcriptional activation. Mujtaba (2002).

== '''Mechanism''' ==

Sandbox Reserved 654: Difference between revisions

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 <Structure load='1jm4' size='500' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' />
-The hydrophobic pocket formed by the loops is the primary binding site for acetyl-lysine proteins. This interaction has been shown via localization and chemical shift experiments that revealed the specific manner with which the bromodomain hydrophobic cavity binds to acetylated lysine residues. Once the acetyl-lysine residue makes the initial binding inside the hydrophobic pocket, the ZA and BC loop residues at the entrance of the pocket interact with the amino acids adjacent (+/- 1 or 2) to the already bound acetyl-lysine. Those interactions reinforce binding of the target sequence. Mujtaba, S. et al (2007) Oncogene 26, 5521. Small structural changes in the conformation of the ZA and BC loops result in exposing other residues that are originally buried within the protein to aid in peptide recognition. Mujtaba, S. et al (2002) Mol. Cell 9, 575.
+Until recently, the function of the bromodomain remained unknown. Its structure and modularity, along with its feature of both N and C termini located together on one end of the protein, suggested that it played a role in protein-protein interactions. It has now been shown that the hydrophobic pocket formed by the loops is the primary binding site for acetyl-lysine proteins, making the bromodomain a functional site for recognition of acetylated lysine residues playing a role in regulation via protein-protein interactions. '''Dhalluin'''. This interaction has been shown via localization and chemical shift experiments that revealed the specific manner with which the bromodomain hydrophobic cavity binds to acetylated lysine residues.
+Once the acetyl-lysine residue makes the initial binding inside the hydrophobic pocket, the ZA and BC loop residues at the entrance of the pocket interact with the amino acids adjacent (+/- 1 or 2) to the already bound acetyl-lysine. Those interactions reinforce binding of the target sequence. Mujtaba, S. et al (2007) Oncogene 26, 5521. Small structural changes in the conformation of the ZA and BC loops result in exposing other residues that are originally buried within the protein to aid in peptide recognition. Mujtaba, S. et al (2002) Mol. Cell 9, 575.
+It is also believed that the bromodomain may also play a role in highly specific histone acetylation by tethering transcriptional HATs to specific chromosomal sites, Brownell, J. et al (1996) Curr. Opin. Genet. Dev. 6, 176, as well as the assembly of multiprotein complexes in transcriptional activation such as the Bromodomain–HIV-1 Tat complex necessary for HIV-1 transcriptional activation. Mujtaba (2002).
 == '''Mechanism''' ==