5ORB

Crystal Structure of BAZ2B bromodomain in complex with 1-methyl-cyclopentapyrazole compound 30

5ORB の概要

• エントリーDOI: 10.2210/pdb5orb/pdb
• 関連するPDBエントリー: 5OR8 5OR9
• 分子名称: Bromodomain adjacent to zinc finger domain protein 2B, 2-(4-methoxyphenyl)sulfanyl-~{N}-(2-methyl-5,6-dihydro-4~{H}-cyclopenta[c]pyrazol-3-yl)ethanamide, 1,2-ETHANEDIOL, ... (4 entities in total)
• 機能のキーワード: four helical bundle, transcription
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Nucleus : Q9UIF8
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 13998.13

構造登録者

Lolli, G.,Dalle Vedove, A.,Marchand, J.-R.,Caflisch, A. (登録日: 2017-08-15, 公開日: 2017-09-13, 最終更新日: 2024-01-17)

主引用文献

Marchand, J.R.,Dalle Vedove, A.,Lolli, G.,Caflisch, A.
Discovery of Inhibitors of Four Bromodomains by Fragment-Anchored Ligand Docking.
J Chem Inf Model, 57:2584-2597, 2017

PubMed Abstract: The high-throughput docking protocol called ALTA-VS (anchor-based library tailoring approach for virtual screening) was developed in 2005 for the efficient in silico screening of large libraries of compounds by preselection of only those molecules that have optimal fragments (anchors) for the protein target. Here we present an updated version of ALTA-VS with a broader range of potential applications. The evaluation of binding energy makes use of a classical force field with implicit solvent in the continuum dielectric approximation. In about 2 days per protein target on a 96-core compute cluster (equipped with Xeon E3-1280 quad core processors at 2.5 GHz), the screening of a library of nearly 77 000 diverse molecules with the updated ALTA-VS protocol has resulted in the identification of 19, 3, 3, and 2 μM inhibitors of the human bromodomains ATAD2, BAZ2B, BRD4(1), and CREBBP, respectively. The success ratio (i.e., number of actives in a competition binding assay in vitro divided by the number of compounds tested) ranges from 8% to 13% in dose-response measurements. The poses predicted by fragment-based docking for the three ligands of the BAZ2B bromodomain were confirmed by protein X-ray crystallography.

PubMed: 28862840
DOI: 10.1021/acs.jcim.7b00336

実験手法

X-RAY DIFFRACTION (2.103 Å)