7ZAT

BRD4 in complex with FragLite20

これはPDB形式変換不可エントリーです。

7ZAT の概要

• エントリーDOI: 10.2210/pdb7zat/pdb
• 分子名称: Isoform C of Bromodomain-containing protein 4, 4-bromanyl-2-(methoxymethyl)pyridine, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: brd4, inhibitor, fragment, bromodomain, fraglite, transcription
• 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: 15588.72

構造登録者

Turberville, S.,Martin, M.P.,Hope, I.,Noble, M.E.M. (登録日: 2022-03-22, 公開日: 2022-11-23, 最終更新日: 2024-01-31)

主引用文献

Davison, G.,Martin, M.P.,Turberville, S.,Dormen, S.,Heath, R.,Heptinstall, A.B.,Lawson, M.,Miller, D.C.,Ng, Y.M.,Sanderson, J.N.,Hope, I.,Wood, D.J.,Cano, C.,Endicott, J.A.,Hardcastle, I.R.,Noble, M.E.M.,Waring, M.J.
Mapping Ligand Interactions of Bromodomains BRD4 and ATAD2 with FragLites and PepLites─Halogenated Probes of Druglike and Peptide-like Molecular Interactions.
J.Med.Chem., 65:15416-15432, 2022

PubMed Abstract: The development of ligands for biological targets is critically dependent on the identification of sites on proteins that bind molecules with high affinity. A set of compounds, called FragLites, can identify such sites, along with the interactions required to gain affinity, by X-ray crystallography. We demonstrate the utility of FragLites in mapping the binding sites of bromodomain proteins BRD4 and ATAD2 and demonstrate that FragLite mapping is comparable to a full fragment screen in identifying ligand binding sites and key interactions. We extend the FragLite set with analogous compounds derived from amino acids (termed PepLites) that mimic the interactions of peptides. The output of the FragLite maps is shown to enable the development of ligands with leadlike potency. This work establishes the use of FragLite and PepLite screening at an early stage in ligand discovery allowing the rapid assessment of tractability of protein targets and informing downstream hit-finding.

PubMed: 36367089
DOI: 10.1021/acs.jmedchem.2c01357

実験手法

X-RAY DIFFRACTION (1.15 Å)