9OIM

The von Hippel Lindau-ElonginB-ElonginC (VCB) complex with fragment 9

これはPDB形式変換不可エントリーです。

9OIM の概要

• エントリーDOI: 10.2210/pdb9oim/pdb
• 分子名称: Elongin-B, Elongin-C, von Hippel-Lindau disease tumor suppressor, ... (6 entities in total)
• 機能のキーワード: vhl, e3 ligase, fragment-based drug discovery, protein transport
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 175799.06

構造登録者

Amporndanai, K.,Katinas, J.M.,Chopra, A.,Fesik, S.W. (登録日: 2025-05-06, 公開日: 2025-07-09, 最終更新日: 2025-09-03)

主引用文献

Amporndanai, K.,Katinas, J.M.,Chopra, A.,Kayode, O.,Vadukoot, A.K.,Waterson, A.G.,Fesik, S.W.
NMR-Based Fragment Screen of the von Hippel-Lindau Elongin C&B Complex.
Acs Med.Chem.Lett., 16:1648-1654, 2025

PubMed Abstract: von Hippel-Lindau (VHL) is an E3 ligase that has been widely exploited for the development of PROTACs to induce degradation of disease-associated target proteins. Nearly all VHL-recruiting PROTACs contain a hydroxyproline moiety based on the endogenous peptide substrate that occupies the HIF1α-binding site of VHL. However, the development of orally bioavailable PROTACs with hydroxyproline-based VHL ligands remains a significant hurdle, due to both the hydroxyproline and the peptidic nature of the VHL ligand. Here, we describe an NMR-based fragment screen against the VHL-Elongin C-Elongin B (VCB) complex. Several hits were shown by X-ray crystallography to bind to the HIF1α active site in VHL of the VCB complex, which opens the possibility for the discovery of new nonhydroxyproline-based VHL ligands for use in VHL-recruiting PROTACs.

PubMed: 40832550
DOI: 10.1021/acsmedchemlett.5c00316

実験手法

X-RAY DIFFRACTION (2.61 Å)