4V32

Cereblon isoform 4 from Magnetospirillum gryphiswaldense in complex with Thalidomide, Y101F mutant

4V32 の概要

• エントリーDOI: 10.2210/pdb4v32/pdb
• 関連するPDBエントリー: 4V2Y 4V2Z 4V30 4V31
• 分子名称: CEREBLON ISOFORM 4, ZINC ION, S-Thalidomide, ... (4 entities in total)
• 機能のキーワード: signaling protein, teratogenicity, aromatic cage
• 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: 42033.64

構造登録者

Hartmann, M.D.,Lupas, A.N.,Hernandez Alvarez, B. (登録日: 2014-10-15, 公開日: 2014-12-17, 最終更新日: 2024-05-08)

主引用文献

Hartmann, M.D.,Boichenko, I.,Coles, M.,Zanini, F.,Lupas, A.N.,Hernandez Alvarez, B.
Thalidomide Mimics Uridine Binding to an Aromatic Cage in Cereblon.
J.Struct.Biol., 188:225-, 2014

PubMed Abstract: Thalidomide and its derivatives lenalidomide and pomalidomide are important anticancer agents but can cause severe birth defects via an interaction with the protein cereblon. The ligand-binding domain of cereblon is found, with a high degree of conservation, in both bacteria and eukaryotes. Using a bacterial model system, we reveal the structural determinants of cereblon substrate recognition, based on a series of high-resolution crystal structures. For the first time, we identify a cellular ligand that is universally present: we show that thalidomide and its derivatives mimic and compete for the binding of uridine, and validate these findings in vivo. The nature of the binding pocket, an aromatic cage of three tryptophan residues, further suggests a role in the recognition of cationic ligands. Our results allow for general evaluation of pharmaceuticals for potential cereblon-dependent teratogenicity.

PubMed: 25448889
DOI: 10.1016/J.JSB.2014.10.010

実験手法

X-RAY DIFFRACTION (1.9 Å)