Structure of BET mutants and tertiary structure of mutants in solution.

<p>(A) Superimposition of wild type BRD2(1) shown as a ribbon diagram with the mutants BRD2(1) R100L and D161Y shown as protein worm in green and magenta, respectively. The mutated residues are shown in ball and stick representation and main structural elements are labelled. (B) Details of interactions formed by R100 in the wild type compared to the mutated residue. (C) Detailed view of BRD2(1) wild type and D161Y. (D) Superimposition of BRD2(2) shown as a ribbon diagram and the mutant BRD2(2) Q443H shown as protein worm in blue. (E) Comparison of the near UV CD spectra of wild type BRD2(1) and all generated mutants. (F) Comparison of the near UV CD spectra of wild type BRD4(1) and the mutants BRD4(1) A89V. (G) Comparison of the near UV CD spectra of wild type BRD2(2) and the mutants BRD2(2) R419W and Q443H. (H) Comparison of the near UV CD spectra of wild type BRD3(2) and the mutants BRD3(2) H395R. (I) Comparison of the near UV CD spectra of wild type BRD4(2) and the mutants BRD4(2) A420D. Near-UV CD spectra were recorded at 20°C in a 1.0-cm quartz cuvette in 20 mM Tris/HCl, pH 7.5 containing 0.20 M NaCl and 2.00 mM DTT, as described in Materials and Methods.