4QZS

Crystal structure of the first bromodomain of human 3-fluoro tyrosine-labeled brd4 in complex with jq1

Summary for 4QZS

• Entry DOI: 10.2210/pdb4qzs/pdb
• Descriptor: Bromodomain-containing protein 4, (6S)-6-(2-tert-butoxy-2-oxoethyl)-4-(4-chlorophenyl)-2,3,9-trimethyl-6,7-dihydrothieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-10-ium, 1,2-ETHANEDIOL, ... (5 entities in total)
• Functional Keywords: cap, mcap, protein binding-inhibitor complex, mitotic chromosome associated protein, cell cycle, inhibitor, transcription
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: O60885
• Total number of polymer chains: 1
• Total formula weight: 15842.89

Authors

Ember, S.W.,Schonbrunn, E. (deposition date: 2014-07-28, release date: 2014-10-29, Last modification date: 2023-09-20)

Primary citation

Mishra, N.K.,Urick, A.K.,Ember, S.W.,Schonbrunn, E.,Pomerantz, W.C.
Fluorinated aromatic amino acids are sensitive (19)f NMR probes for bromodomain-ligand interactions.
Acs Chem.Biol., 9:2755-2760, 2014

PubMed Abstract: 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.

PubMed: 25290579
DOI: 10.1021/cb5007344

Experimental method

X-RAY DIFFRACTION (1.45 Å)