5AMI

Cereblon isoform 4 from Magnetospirillum gryphiswaldense in complex with Thalidomide, Wash I structure

5AMI の概要

• エントリーDOI: 10.2210/pdb5ami/pdb
• 関連するPDBエントリー: 5AMH 5AMJ 5AMK
• 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: 41823.42

構造登録者

Hartmann, M.D.,Lupas, A.N.,Hernandez Alvarez, B. (登録日: 2015-03-10, 公開日: 2015-07-01, 最終更新日: 2024-01-10)

主引用文献

Hartmann, M.D.,Boichenko, I.,Coles, M.,Lupas, A.N.,Hernandez Alvarez, B.
Structural Dynamics of the Cereblon Ligand Binding Domain.
Plos One, 10:28342-, 2015

PubMed Abstract: Cereblon, a primary target of thalidomide and its derivatives, has been characterized structurally from both bacteria and animals. Especially well studied is the thalidomide binding domain, CULT, which shows an invariable structure across different organisms and in complex with different ligands. Here, based on a series of crystal structures of a bacterial representative, we reveal the conformational flexibility and structural dynamics of this domain. In particular, we follow the unfolding of large fractions of the domain upon release of thalidomide in the crystalline state. Our results imply that a third of the domain, including the thalidomide binding pocket, only folds upon ligand binding. We further characterize the structural effect of the C-terminal truncation resulting from the mental-retardation linked R419X nonsense mutation in vitro and offer a mechanistic hypothesis for its irresponsiveness to thalidomide. At 1.2Å resolution, our data provide a view of thalidomide binding at atomic resolution.

PubMed: 26024445
DOI: 10.1371/JOURNAL.PONE.0128342

実験手法

X-RAY DIFFRACTION (1.75 Å)