5FH7

Crystal structure of the fifth bromodomain of human PB1 in complex with compound 18

5FH7 の概要

• エントリーDOI: 10.2210/pdb5fh7/pdb
• 分子名称: Protein polybromo-1, 1,2-ETHANEDIOL, 6-chloranyl-3-[(dimethylamino)methyl]-4~{H}-pyrrolo[1,2-a]quinazolin-5-one, ... (4 entities in total)
• 機能のキーワード: pbrm1, brg1-associated factor 180, transcription, chromatin remodeling
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Nucleus: Q86U86
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 29971.60

構造登録者

Tallant, C.,Sutherell, C.L.,Siejka, P.,Sorrell, F.J.,Krojer, T.,Picaud, S.,Fedorov, O.,von Delft, F.,Arrowsmith, C.H.,Edwards, A.M.,Bountra, C.,Brennan, P.E.,Ley, S.V.,Knapp, S. (登録日: 2015-12-21, 公開日: 2016-06-01, 最終更新日: 2024-01-10)

主引用文献

Sutherell, C.L.,Tallant, C.,Monteiro, O.P.,Yapp, C.,Fuchs, J.E.,Fedorov, O.,Siejka, P.,Muller, S.,Knapp, S.,Brenton, J.D.,Brennan, P.E.,Ley, S.V.
Identification and Development of 2,3-Dihydropyrrolo[1,2-a]quinazolin-5(1H)-one Inhibitors Targeting Bromodomains within the Switch/Sucrose Nonfermenting Complex.
J.Med.Chem., 59:5095-5101, 2016

PubMed Abstract: Bromodomain containing proteins PB1, SMARCA4, and SMARCA2 are important components of SWI/SNF chromatin remodeling complexes. We identified bromodomain inhibitors that target these proteins and display unusual binding modes involving water displacement from the KAc binding site. The best compound binds the fifth bromodomain of PB1 with a KD of 124 nM, SMARCA2B and SMARCA4 with KD values of 262 and 417 nM, respectively, and displays excellent selectivity over bromodomains other than PB1, SMARCA2, and SMARCA4.

PubMed: 27119626
DOI: 10.1021/acs.jmedchem.5b01997

実験手法

X-RAY DIFFRACTION (1.47 Å)