5AMH

Cereblon isoform 4 from Magnetospirillum gryphiswaldense in complex with Thalidomide, trigonal crystal form

Summary for 5AMH

• Entry DOI: 10.2210/pdb5amh/pdb
• Related: 5AMI 5AMJ 5AMK
• Descriptor: CEREBLON ISOFORM 4, ZINC ION, S-Thalidomide, ... (7 entities in total)
• Functional Keywords: signaling protein, teratogenicity, aromatic cage
• Biological source: MAGNETOSPIRILLUM GRYPHISWALDENSE
• Total number of polymer chains: 1
• Total formula weight: 14374.16

Authors

Hartmann, M.D.,Lupas, A.N.,Hernandez Alvarez, B. (deposition date: 2015-03-10, release date: 2015-07-01, Last modification date: 2024-01-10)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.2 Å)