6GMR

pVHL:EloB:EloC in complex with (4-(1H-pyrrol-1-yl)phenyl)methanol

6GMR の概要

• エントリーDOI: 10.2210/pdb6gmr/pdb
• 分子名称: Elongin-B, Elongin-C, Hypoxia inducible factor 1alpha, residues 559-577, ... (8 entities in total)
• 機能のキーワード: e3 ubiquitin ligase, von hippel lindau tumor supressor, protoc, fragment-based drug discovery, ligase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 45584.66

構造登録者

Van Molle, I.,Lucas, X.,Ciulli, A. (登録日: 2018-05-28, 公開日: 2018-08-08, 最終更新日: 2018-09-05)

主引用文献

Lucas, X.,Van Molle, I.,Ciulli, A.
Surface Probing by Fragment-Based Screening and Computational Methods Identifies Ligandable Pockets on the von Hippel-Lindau (VHL) E3 Ubiquitin Ligase.
J. Med. Chem., 61:7387-7393, 2018

PubMed Abstract: Beyond the targeting of E3 ubiquitin ligases to inhibit protein homeostasis, E3 ligase binders can be repurposed as targeted protein degraders (PROTACs or molecular glues). We sought to identify new binders of the VHL E3 ligase by biophysical fragment-based screening followed by X-ray crystallographic soaking. We identified fragments binding at the ElonginC:Cullin2 interface and a new cryptic pocket in VHL, along with other potential ligandable sites predicted computationally and found to bind solvent molecules in crystal structures. The elucidated interactions provide starting points for future ligand development.

PubMed: 30040896
DOI: 10.1021/acs.jmedchem.8b00842

実験手法

X-RAY DIFFRACTION (1.75 Å)