6FGH

Crystal Structure of BAZ2A bromodomain in complex with 3-amino-2-methylpyridine derivative 1

Summary for 6FGH

• Entry DOI: 10.2210/pdb6fgh/pdb
• Related: 5L8T 5L96
• Descriptor: Bromodomain adjacent to zinc finger domain protein 2A, 2-methyl-~{N}-[(2~{R})-1-methylsulfonylpropan-2-yl]pyridin-3-amine (3 entities in total)
• Functional Keywords: four helical bundle, transcription
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 12609.23

Authors

Dalle Vedove, A.,Marchand, J.-R.,Lolli, G.,Caflisch, A. (deposition date: 2018-01-10, release date: 2018-05-30, Last modification date: 2024-01-17)

Primary citation

Dalle Vedove, A.,Spiliotopoulos, D.,D'Agostino, V.G.,Marchand, J.R.,Unzue, A.,Nevado, C.,Lolli, G.,Caflisch, A.
Structural Analysis of Small-Molecule Binding to the BAZ2A and BAZ2B Bromodomains.
ChemMedChem, 13:1479-1487, 2018

PubMed Abstract: The bromodomain-containing protein BAZ2A is a validated target in prostate cancer research, whereas the function of its paralogue BAZ2B is still undefined. The bromodomains of BAZ2A and BAZ2B have a similar binding site for their natural ligand, the acetylated lysine side chain. Here, we present an analysis of the binding modes of eight compounds belonging to three distinct chemical classes. For all compounds, the moiety mimicking the natural ligand engages in essentially identical interactions in the BAZ2A and BAZ2B bromodomains. In contrast, the rest of the molecule is partially solvent-exposed and adopts different orientations with different interactions in the two bromodomains. Some of these differences could be exploited for designing inhibitors with selectivity within the BAZ2 bromodomain subfamily.

PubMed: 29770599
DOI: 10.1002/cmdc.201800234

Experimental method

X-RAY DIFFRACTION (2.1 Å)