Peregrin: Difference between revisions

The BRPF1 bromodomain has been shown to recognize and bind to various acetylated lysine marks on the N-terminal tails of histones tails <ref name="Glass1" />. It preferentially binds to histone H4 acetylated at positions K5 ([[2rs9]]), K8, and K12 ([[4qyd]]) as well as H3 and H2A (([[4qyl]]) at position K14 and K5, respectively<ref name="Obi" />,<ref name="Glass1" />. Interestingly, the BRPF1 bromodomain has also been shown to bind di-acetylated histone peptides as a monomer with high affinity, including H4K5acK8ac and H4K5acK12ac <ref name="Obi" />. Acetyllysine recognition is coordinated by a number of residues in the bromodomain's binding pocket. Using NMR chemical shift perturbation experiments, Glass et al. reported several <scene name='91/910741/Nmr_resi_h4_binding/1'>key residues</scene> the undergo conformational changes upon histone H4 ligand binding (I27, L34, E36, V37, N83, and I88)<ref name="Obi" />. Notably, asparagine 83 was among these. The interaction between the amide nitrogen of asparagine with the carbonyl of the acetyllysine group is conserved in all bromodomains and is necessary for binding to occur <ref name ="Obi" />,<ref name ="Lubula_2014" />. Furthermore, the tyrosine 40 and isoleucine 27 stabilize the acetyllysine residue through water-mediated hydrogen bonds<ref name="Lubula_2014" />.