6UML

Structural Basis for Thalidomide Teratogenicity Revealed by the Cereblon-DDB1-SALL4-Pomalidomide Complex

6UML の概要

• エントリーDOI: 10.2210/pdb6uml/pdb
• 分子名称: DNA damage-binding protein 1, Protein cereblon, Sal-like protein 4, ... (5 entities in total)
• 機能のキーワード: celmod, cereblon-crl4, ubiquitin ligase, c2h2 zinc finger, ligase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 177358.87

構造登録者

Clayton, T.L.,Matyskiela, M.E.,Pagarigan, B.E.,Tran, E.T.,Chamberlain, P.P. (登録日: 2019-10-09, 公開日: 2020-04-15, 最終更新日: 2024-11-06)

主引用文献

Matyskiela, M.E.,Clayton, T.,Zheng, X.,Mayne, C.,Tran, E.,Carpenter, A.,Pagarigan, B.,McDonald, J.,Rolfe, M.,Hamann, L.G.,Lu, G.,Chamberlain, P.P.
Crystal structure of the SALL4-pomalidomide-cereblon-DDB1 complex.
Nat.Struct.Mol.Biol., 27:319-322, 2020

PubMed Abstract: Thalidomide-dependent degradation of the embryonic transcription factor SALL4 by the CRL4 E3 ubiquitin ligase is a plausible major driver of thalidomide teratogenicity. The structure of the second zinc finger of SALL4 in complex with pomalidomide, cereblon and DDB1 reveals the molecular details of recruitment. Sequence differences and a shifted binding position relative to Ikaros offer a path to the rational design of cereblon-binding drugs with reduced teratogenic risk.

PubMed: 32251415
DOI: 10.1038/s41594-020-0405-9

実験手法

X-RAY DIFFRACTION (3.58 Å)