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Does bromodomain flexibility influence histone recognition?
Author(s) -
Steiner Sandra,
Magno Andrea,
Huang Danzhi,
Caflisch Amedeo
Publication year - 2013
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2013.05.032
Subject(s) - bromodomain , histone , acetylation , flexibility (engineering) , binding site , chemistry , computational biology , nucleosome , biophysics , lysine , molecular dynamics , plasma protein binding , biochemistry , biology , microbiology and biotechnology , amino acid , dna , computational chemistry , mathematics , gene , statistics
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.