A bromodomain is an approximately 110 amino acid protein domain that recognizes monoacetylated lysine residues such as those on the N-terminal tails of histones. Their affinity is higher for regions where multiple acetylation sites exist in proximity. This recognition is often a prerequisite for protein-histone association and chromatin remodeling. The domain itself adopts an all-α protein fold, a bundle of four alpha helices each separated by loop regions of variable lengths that form a hydrophobic pocket that recognizes the acetyl lysine.
In humans there are 46 sets of chromatins that contain a total of 61 bromodomains. A well-known example of a bromodomain family is the BET (Bromodomain and extraterminal domain family). Members of this family include BRD2, BRD3, BRD4 and BRDT. However proteins such as ASH1L also contain a bromodomain. Dysfunction of BRD proteins has been linked to diseases such as human squamous cell carcinoma and other forms of cancer.
Small molecule inhibition
Members of the BET family have been implicated as targets in human cancer. These BET inhibitors have shown therapeutic effects in multiple preclinical models of cancer and are currently in clinical trials in the United States.
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