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)
Summary for 6VEO
| Entry DOI | 10.2210/pdb6veo/pdb |
| Descriptor | 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) |
| Functional Keywords | bromodomain, epigenetics, nuclear protein |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 16529.85 |
| Authors | Glass, K.C. (deposition date: 2020-01-02, release date: 2020-10-28, Last modification date: 2023-10-11) |
| Primary citation | 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 Cited by 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: 33084328DOI: 10.1021/acs.jmedchem.0c01178 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.4 Å) |
Structure validation
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