5E9M

Crystal Structure of BAZ2B bromodomain in complex with N-methyltrimethylacetamide

Summary for 5E9M

• Entry DOI: 10.2210/pdb5e9m/pdb
• Related: 4IOO 5DYU 5DYX 5E9I 5E9K 5E9L
• Descriptor: Bromodomain adjacent to zinc finger domain protein 2B, N-methyltrimethylacetamide (3 entities in total)
• Functional Keywords: four helical bundle, transcription
• Biological source: Homo sapiens (Human)
• Cellular location: Nucleus : Q9UIF8
• Total number of polymer chains: 1
• Total formula weight: 13646.75

Authors

Lolli, G.,Caflisch, A. (deposition date: 2015-10-15, release date: 2016-03-16, Last modification date: 2024-01-10)

Primary citation

Lolli, G.,Caflisch, A.
High-Throughput Fragment Docking into the BAZ2B Bromodomain: Efficient in Silico Screening for X-Ray Crystallography.
Acs Chem.Biol., 11:800-807, 2016

PubMed Abstract: Bromodomains are protein modules that bind to acetylated lysine side chains in histones and other proteins. The bromodomain adjacent to zinc finger domain protein 2B (BAZ2B) has been reported to be poorly druggable. Here, we screened an in-house library of 350 fragments by automatic docking to the BAZ2B bromodomain. The top 12 fragments according to the predicted binding energy were selected for experiments of soaking into apo crystals of BAZ2B which yielded the structure of the complex for four of them, which is a hit rate of 33%. Additional crystal structures were solved for BAZ2B and two scaffolds identified by analogy. For three topologically similar fragments, the crystal structures reveal binding modes with different penetration, i.e., with zero, one, and two water molecules, respectively, located between the fragment and the side chain of a conserved tyrosine (Tyr1901) in the bottom of the acetyl lysine pocket of BAZ2B. Furthermore, a remarkable stereoselectivity of the acetyl lysine pocket emerges from the crystal structures of the bromodomains of BAZ2B and SMARCA4 in complex with the chiral diol MPD (2-methyl-2,4-pentanediol).

PubMed: 26942307
DOI: 10.1021/acschembio.5b00914

Experimental method

X-RAY DIFFRACTION (1.778 Å)