4NRA

Crystal Structure of the bromodomain of human BAZ2B in complex with compound-6 E11322

Summary for 4NRA

• Entry DOI: 10.2210/pdb4nra/pdb
• Related: 4NR9 4NRB 4NRC
• Descriptor: Bromodomain adjacent to zinc finger domain protein 2B, 1,2-ETHANEDIOL, 1-(8-chloro-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl)ethanone, ... (4 entities in total)
• Functional Keywords: sgc, structural genomics consortium, transcription, bromodomain, acetylated lysine binding protein, kiaa1476, walp4
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus (Potential): Q9UIF8
• Total number of polymer chains: 1
• Total formula weight: 14177.70

Authors

Chaikuad, A.,Felletar, I.,Ferguson, F.M.,Filippakopoulos, P.,Fedorov, O.,von Delft, F.,Arrowsmith, C.H.,Edwards, A.M.,Bountra, C.,Knapp, S.,Structural Genomics Consortium (SGC) (deposition date: 2013-11-26, release date: 2013-12-25, Last modification date: 2023-09-20)

Primary citation

Ferguson, F.M.,Fedorov, O.,Chaikuad, A.,Philpott, M.,Muniz, J.R.,Felletar, I.,von Delft, F.,Heightman, T.,Knapp, S.,Abell, C.,Ciulli, A.
Targeting low-druggability bromodomains: fragment based screening and inhibitor design against the BAZ2B bromodomain.
J.Med.Chem., 56:10183-10187, 2013

PubMed Abstract: Bromodomains are epigenetic reader domains that have recently become popular targets. In contrast to BET bromodomains, which have proven druggable, bromodomains from other regions of the phylogenetic tree have shallower pockets. We describe successful targeting of the challenging BAZ2B bromodomain using biophysical fragment screening and structure-based optimization of high ligand-efficiency fragments into a novel series of low-micromolar inhibitors. Our results provide attractive leads for development of BAZ2B chemical probes and indicate the whole family may be tractable.

PubMed: 24304323
DOI: 10.1021/jm401582c

Experimental method

X-RAY DIFFRACTION (1.85 Å)