6ZN6

Protein polybromo-1 (PB1 BD2) Bound To MW278

Summary for 6ZN6

• Entry DOI: 10.2210/pdb6zn6/pdb
• Descriptor: Protein polybromo-1, 2-[6-azanyl-5-[(3~{R})-3-phenoxypiperidin-1-yl]pyridazin-3-yl]phenol, 1,2-ETHANEDIOL, ... (4 entities in total)
• Functional Keywords: bromodomain inhibitor epigenetics, protein binding
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 27249.52

Authors

Preuss, F.,Mathea, S.,Chatterjee, D.,Wanior, M.,Joerger, A.C.,Knapp, S. (deposition date: 2020-07-06, release date: 2020-08-26, Last modification date: 2024-01-31)

Primary citation

Wanior, M.,Preuss, F.,Ni, X.,Kramer, A.,Mathea, S.,Gobel, T.,Heidenreich, D.,Simonyi, S.,Kahnt, A.S.,Joerger, A.C.,Knapp, S.
Pan-SMARCA/PB1 Bromodomain Inhibitors and Their Role in Regulating Adipogenesis.
J.Med.Chem., 63:14680-14699, 2020

PubMed Abstract: Accessibility of the human genome is modulated by the ATP-driven SWI/SNF chromatin remodeling multiprotein complexes BAF (BRG1/BRM-associated factor) and PBAF (polybromo-associated BAF factor), which involves reading of acetylated histone tails by the bromodomain-containing proteins SMARCA2 (BRM), SMARCA4 (BRG1), and polybromo-1. Dysregulation of chromatin remodeling leads to aberrant cell proliferation and differentiation. Here, we have characterized a set of potent and cell-active bromodomain inhibitors with pan-selectivity for canonical family VIII bromodomains. Targeted SWI/SNF bromodomain inhibition blocked the expression of key genes during adipogenesis, including the transcription factors PPARγ and C/EBPα, and impaired the differentiation of 3T3-L1 murine fibroblasts into adipocytes. Our data highlight the role of SWI/SNF bromodomains in adipogenesis and provide a framework for the development of SWI/SNF bromodomain inhibitors for indirect targeting of key transcription factors regulating cell differentiation.

PubMed: 33216538
DOI: 10.1021/acs.jmedchem.0c01242

Experimental method

X-RAY DIFFRACTION (2.02 Å)