4XUB

Crystal Structure of the bromodomain of human BAZ2B in complex with BAZ2-ICR chemical probe

Summary for 4XUB

• Entry DOI: 10.2210/pdb4xub/pdb
• Related: 4XUA
• Descriptor: Bromodomain adjacent to zinc finger domain protein 2B, 4-{4-(1-methyl-1H-pyrazol-4-yl)-1-[2-(4-methyl-1H-1,2,3-triazol-1-yl)ethyl]-1H-imidazol-5-yl}benzonitrile, 1,2-ETHANEDIOL, ... (4 entities in total)
• Functional Keywords: transcription, bromodomain, acetylated lysine binding protein, kiaa1476, walp4, sgc, structural genomics consortium
• Biological source: Homo sapiens (Human)
• Cellular location: Nucleus : Q9UIF8
• Total number of polymer chains: 1
• Total formula weight: 14163.26

Authors

Chaikuad, A.,Felletar, I.,von Delft, F.,Arrowsmith, C.H.,Edwards, A.M.,Bountra, C.,Knapp, S.,Structural Genomics Consortium (SGC) (deposition date: 2015-01-25, release date: 2015-03-11, Last modification date: 2024-01-10)

Primary citation

Drouin, L.,McGrath, S.,Vidler, L.R.,Chaikuad, A.,Monteiro, O.,Tallant, C.,Philpott, M.,Rogers, C.,Fedorov, O.,Liu, M.,Akhtar, W.,Hayes, A.,Raynaud, F.,Muller, S.,Knapp, S.,Hoelder, S.
Structure Enabled Design of BAZ2-ICR, A Chemical Probe Targeting the Bromodomains of BAZ2A and BAZ2B.
J.Med.Chem., 58:2553-2559, 2015

PubMed Abstract: The bromodomain containing proteins BAZ2A/B play essential roles in chromatin remodeling and regulation of noncoding RNAs. We present the structure based discovery of a potent, selective, and cell active inhibitor 13 (BAZ2-ICR) of the BAZ2A/B bromodomains through rapid optimization of a weakly potent starting point. A key feature of the presented inhibitors is an intramolecular aromatic stacking interaction that efficiently occupies the shallow bromodomain pockets. 13 represents an excellent chemical probe for functional studies of the BAZ2 bromodomains in vitro and in vivo.

PubMed: 25719566
DOI: 10.1021/jm501963e

Experimental method

X-RAY DIFFRACTION (1.98 Å)