6FI1

Crystal structure of human BAZ2B PHD zinc finger in complex with Fr23

6FI1 の概要

• エントリーDOI: 10.2210/pdb6fi1/pdb
• 分子名称: Bromodomain adjacent to zinc finger domain protein 2B, ZINC ION, ~{N}-(4-aminophenyl)-2-azanyl-ethanamide (3 entities in total)
• 機能のキーワード: transcription, phd, zinc finger, baz2b, baz2a, bromodomain, fragment, epigenetic
• 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: 2
• 化学式量合計: 13514.24

構造登録者

Amato, A.,Lucas, X.,Bortoluzzi, A.,Wright, D.,Ciulli, A. (登録日: 2018-01-16, 公開日: 2018-03-21, 最終更新日: 2024-01-17)

主引用文献

Amato, A.,Lucas, X.,Bortoluzzi, A.,Wright, D.,Ciulli, A.
Targeting Ligandable Pockets on Plant Homeodomain (PHD) Zinc Finger Domains by a Fragment-Based Approach.
ACS Chem. Biol., 13:915-921, 2018

PubMed Abstract: Plant homeodomain (PHD) zinc fingers are histone reader domains that are often associated with human diseases. Despite this, they constitute a poorly targeted class of readers, suggesting low ligandability. Here, we describe a successful fragment-based campaign targeting PHD fingers from the proteins BAZ2A and BAZ2B as model systems. We validated a pool of in silico fragments both biophysically and structurally and solved the first crystal structures of PHD zinc fingers in complex with fragments bound to an anchoring pocket at the histone binding site. The best-validated hits were found to displace a histone H3 tail peptide in competition assays. This work identifies new chemical scaffolds that provide suitable starting points for future ligand optimization using structure-guided approaches. The demonstrated ligandability of the PHD reader domains could pave the way for the development of chemical probes to drug this family of epigenetic readers.

PubMed: 29529862
DOI: 10.1021/acschembio.7b01093

実験手法

X-RAY DIFFRACTION (2.7 Å)