TY - JOUR KW - Hydrogen Bonding KW - Protein Structure, Secondary KW - Protein Binding KW - Binding Sites KW - DNA-Binding Proteins KW - Nuclear Proteins KW - Protein Processing, Post-Translational KW - Protein Interaction Domains and Motifs KW - Chromosomal Proteins, Non-Histone KW - Histones KW - Molecular Dynamics Simulation KW - Acetylation KW - Adenosine Triphosphatases KW - Amino Acid Motifs KW - CREB-Binding Protein KW - DNA Helicases KW - Histone Acetyltransferases KW - TATA-Binding Protein Associated Factors KW - Transcription Factor TFIID KW - Transcription Factors AU - S. Steiner AU - A. Magno AU - D. Huang AU - A. Caflisch AB -

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.

BT - FEBS Letters C1 - 0173 DA - 2013 Jul 11 DO - 10.1016/j.febslet.2013.05.032 IS - 14 J2 - FEBS Lett. LA - eng M3 - Research Article N2 -

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.

PY - 2013 SP - 2158 EP - 2163 T2 - FEBS Letters TI - Does bromodomain flexibility influence histone recognition? VL - 587 SN - 1873-3468 ER -