6VEO

ATAD2B bromodomain in complex with 4-({[(3R,4R)-4-{[3-methyl-5-(5-methylpyridin-3-yl)-2-oxo-1,2-dihydro-1,7-naphthyridin-8-yl]amino}piperidin-3-yl]oxy}methyl)-1lambda~6~-thiane-1,1-dione (compound 38)

6VEO の概要

• エントリーDOI: 10.2210/pdb6veo/pdb
• 分子名称: ATPase family AAA domain-containing protein 2B, SULFATE ION, 4-({[(3R,4R)-4-{[3-methyl-5-(5-methylpyridin-3-yl)-2-oxo-1,2-dihydro-1,7-naphthyridin-8-yl]amino}piperidin-3-yl]oxy}methyl)-1lambda~6~-thiane-1,1-dione, ... (4 entities in total)
• 機能のキーワード: bromodomain, epigenetics, nuclear protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 16529.85

構造登録者

Glass, K.C. (登録日: 2020-01-02, 公開日: 2020-10-28, 最終更新日: 2023-10-11)

主引用文献

Lloyd, J.T.,McLaughlin, K.,Lubula, M.Y.,Gay, J.C.,Dest, A.,Gao, C.,Phillips, M.,Tonelli, M.,Cornilescu, G.,Marunde, M.R.,Evans, C.M.,Boyson, S.P.,Carlson, S.,Keogh, M.C.,Markley, J.L.,Frietze, S.,Glass, K.C.
Structural Insights into the Recognition of Mono- and Diacetylated Histones by the ATAD2B Bromodomain.
J.Med.Chem., 63:12799-12813, 2020

PubMed Abstract: Bromodomains exhibit preferences for specific patterns of post-translational modifications on core and variant histone proteins. We examined the ligand specificity of the ATAD2B bromodomain and compared it to its closely related paralogue in ATAD2. We show that the ATAD2B bromodomain recognizes mono- and diacetyllysine modifications on histones H4 and H2A. A structure-function approach was used to identify key residues in the acetyllysine-binding pocket that dictate the molecular recognition process, and we examined the binding of an ATAD2 bromodomain inhibitor by ATAD2B. Our analysis demonstrated that critical contacts required for bromodomain inhibitor coordination are conserved between the ATAD2/B bromodomains, with many residues playing a dual role in acetyllysine recognition. We further characterized an alternative splice variant of ATAD2B that results in a loss of function. Our results outline the structural and functional features of the ATAD2B bromodomain and identify a novel mechanism regulating the interaction of the ATAD2B protein with chromatin.

PubMed: 33084328
DOI: 10.1021/acs.jmedchem.0c01178

実験手法

X-RAY DIFFRACTION (2.4 Å)