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PDBsum entry 4qzs
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Transcription
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PDB id
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4qzs
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References listed in PDB file
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Key reference
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Title
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Fluorinated aromatic amino acids are sensitive 19f nmr probes for bromodomain-Ligand interactions.
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Authors
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N.K.Mishra,
A.K.Urick,
S.W.Ember,
E.Schönbrunn,
W.C.Pomerantz.
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Ref.
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Acs Chem Biol, 2014,
9,
2755-2760.
[DOI no: ]
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PubMed id
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Abstract
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We describe a (19)F NMR method for detecting bromodomain-ligand interactions
using fluorine-labeled aromatic amino acids due to the conservation of aromatic
residues in the bromodomain binding site. We test the sensitivity, accuracy, and
speed of this method with small molecule ligands (+)-JQ1, BI2536, Dinaciclib,
TG101348, and acetaminophen using three bromodomains Brd4, BrdT, and BPTF.
Simplified (19)F NMR spectra allowed for simultaneous testing of multiple
bromodomains to assess selectivity and identification of a new BPTF ligand.
Fluorine labeling only modestly affected the Brd4 structure and function
assessed by isothermal titration calorimetry, circular dichroism, and X-ray
crystallography. The speed, ease of interpretation, and low concentration of
protein needed for binding experiments affords a new method to discover and
characterize both native and new ligands.
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