7PSO

Cereblon isoform 4 from Magnetospirillum gryphiswaldense in complex with Avadomide (CC-122)

7PSO の概要

• エントリーDOI: 10.2210/pdb7pso/pdb
• 関連するPDBエントリー: 7PS9
• 分子名称: Cereblon isoform 4, ZINC ION, S-Thalidomide, ... (6 entities in total)
• 機能のキーワード: immunomodulatory imide drug, ubiquitin ligase, protein degradation, signaling protein
• 由来する生物種: Magnetospirillum gryphiswaldense
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 42181.38

構造登録者

Heim, C.,Hartmann, M.D. (登録日: 2021-09-23, 公開日: 2022-03-16, 最終更新日: 2024-01-31)

主引用文献

Heim, C.,Hartmann, M.D.
High-resolution structures of the bound effectors avadomide (CC-122) and iberdomide (CC-220) highlight advantages and limitations of the MsCI4 soaking system.
Acta Crystallogr D Struct Biol, 78:290-298, 2022

PubMed Abstract: Cereblon (CRBN) is the substrate receptor of the CRL4 E3 ubiquitin ligase and is a central player in targeted protein degradation. It is the target of the thalidomide-derived immunomodulatory drugs (IMiDs) and is one of the most widely employed receptors for proteolysis-targeting chimeras (PROTACs), both of which induce the ubiquitination and subsequent proteasomal degradation of target proteins. Structural studies of ligand binding to CRBN are crucial to elucidate the mechanisms of action and for mediation of side effects, ultimately aiding the development of next-generation IMiDs and PROTACs. With this aim, a crystal-soaking system based on the single-domain bacterial homologue MsCI4 has previously been established and used to delineate the binding modes of several classes of small molecules, including FDA-approved drugs, at the molecular level. Here, this system was used to characterize the binding of the next-generation IMiDs avadomide (CC-122) and iberdomide (CC-220) at high resolution, highlighting the advantages and limitations of the MsCI4 system and its implications for the development of future cereblon effectors.

PubMed: 35234143
DOI: 10.1107/S2059798322000092

実験手法

X-RAY DIFFRACTION (1.52 Å)