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Does bromodomain flexibility influence histone recognition?

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S. Steiner; A. Magno; D. Huang; A. Caflisch

Journal: FEBS Lett.
Year: 2013
Volume: 587
Issue: 14
Pages: 2158-2163
DOI: 10.1016/j.febslet.2013.05.032
Type of Publication: Journal Article

Acetylation; Adenosine Triphosphatases; Amino Acid Motifs; Binding Sites; Chromosomal Proteins, Non-Histone; CREB-Binding Protein; DNA Helicases; DNA-Binding Proteins; Histone Acetyltransferases; Histones; Hydrogen Bonding; Molecular Dynamics Simulation; Nuclear Proteins; Protein Binding; Protein Interaction Domains and Motifs; Protein Processing, Post-Translational; Protein Structure, Secondary; TATA-Binding Protein Associated Factors; Transcription Factor TFIID; Transcription Factors


Bromodomains are protein modules that selectively recognize histones by binding to acetylated lysines. Here, we have carried out multiple molecular dynamics simulations of 20 human bromodomains to investigate the flexibility of their binding site. Some bromodomains show alternative side chain orientations of three evolutionarily conserved residues: the Asn involved in acetyl-lysine binding and two conserved aromatic residues. Furthermore, for the BAZ2B and CREBBP bromodomains we observe occlusion of the binding site which is coupled to the displacement of the two aromatic residues. In contrast to available structures, the simulations reveal large variability of the binding site accessibility. The simulations suggest that the flexibility of the bromodomain binding site and presence of self-occluded metastable states influence the recognition of acetyl-lysine on histone tails.