Crystal structure of the first bromodomain (BD1) of human BRD4 in complex with dual BRD4-JAK2 inhibitor MA9-086

Structure

x-ray diffraction · 2 distinct chains · 53% helix, 0% strand (DSSP).

Ligands and binding sites

• R6S · N~4~-[1-(tert-butylsulfonyl)-2,3-dihydro-1H-indol-6-yl]-N~2~-[3-fluoro-4-(1-methylpiperidin-4-yl)phenyl]-5-methylpyrimidine-2,4-diamine · ligand · 2 copies · chains A, B
• EDO · 1,2-ethanediol · additive · 6 copies · chains A, B

Binding sites are the residues within 4.5 Å of a ligand's heavy atoms.

Pockets

3 pockets found on a 1 Å grid, 3 with a druggability of 0.5 or more.

Interfaces

1 interface between chains.

• A–B · 522 Ų buried · 6 hydrogen bonds · protein-protein

Compared structures

• 7REK · Crystal structure of the first bromodomain (BD1) of human BRD4 in complex with dual… · the same entry in another collection · chain B against B, TM-score 1.00
• O60885 · AlphaFold monomer V2.0 prediction for bromodomain-containing protein 4 (O60885) · a predicted model of the same protein · chain A against A, TM-score 0.98

Analyse

• Open in the research workbench: secondary structure, accessibility, pockets, interfaces, conservation, variants, modifications, peptides and crosslinks on the 3D structure
• Every structure of UniProt O60885
• Elsewhere: RCSB PDB 7REK · PDBe 7REK · UniProt O60885