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PDBsum entry 5dyu
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Transcription
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PDB id
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5dyu
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References listed in PDB file
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Key reference
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Title
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High-Throughput fragment docking into the baz2b bromodomain: efficient in silico screening for X-Ray crystallography.
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Authors
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G.Lolli,
A.Caflisch.
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Ref.
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Acs Chem Biol, 2016,
11,
800-807.
[DOI no: ]
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PubMed id
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Abstract
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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).
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