5M3A

Crystal structure of BRD4 BROMODOMAIN 1 IN COMPLEX WITH LIGAND 2

5M3A の概要

• エントリーDOI: 10.2210/pdb5m3a/pdb
• 分子名称: Bromodomain-containing protein 4, 1,2-ETHANEDIOL, 3-methyl-6-(1-methyl-5-phenoxy-pyrazol-4-yl)-[1,2,4]triazolo[4,3-b]pyridazine, ... (4 entities in total)
• 機能のキーワード: bromodomain, brd4 bd1, epigenetic, histone reader, transcription
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Nucleus: O60885
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 15529.84

構造登録者

Kessler, D.,Mayer, M.,Engelhardt, H.,Wolkerstorfer, B.,Geist, L. (登録日: 2016-10-14, 公開日: 2017-09-27, 最終更新日: 2024-01-17)

主引用文献

Geist, L.,Mayer, M.,Cockcroft, X.L.,Wolkerstorfer, B.,Kessler, D.,Engelhardt, H.,McConnell, D.B.,Konrat, R.
Direct NMR Probing of Hydration Shells of Protein Ligand Interfaces and Its Application to Drug Design.
J. Med. Chem., 60:8708-8715, 2017

PubMed Abstract: Fragment-based drug design exploits initial screening of low molecular weight compounds and their concomitant affinity improvement. The multitude of possible chemical modifications highlights the necessity to obtain structural information about the binding mode of a fragment. Herein we describe a novel NMR methodology (LOGSY titration) that allows the determination of binding modes of low affinity binders in the protein-ligand interface and reveals suitable ligand positions for the addition of functional groups that either address or substitute protein-bound water, information of utmost importance for drug design. The particular benefit of the methodology and in contrast to conventional ligand-based methods is the independence of the molecular weight of the protein under study. The validity of the novel approach is demonstrated on two ligands interacting with bromodomain 1 of bromodomain containing protein 4, a prominent cancer target in pharmaceutical industry.

PubMed: 28910100
DOI: 10.1021/acs.jmedchem.7b00845

実験手法

X-RAY DIFFRACTION (1.65 Å)