4v32

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

spinqualitylabelsall models 4v32, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4v32 is a 3 chain structure with sequence from Magnetospirillum gryphiswaldense MSR-1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.9Å Ligands: EF2, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A4TVL0_9PROT Publication Abstract from PubMed 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. Thalidomide mimics uridine binding to an aromatic cage in cereblon.,Hartmann MD, Boichenko I, Coles M, Zanini F, Lupas AN, Hernandez Alvarez B J Struct Biol. 2014 Nov 4;188(3):225-232. doi: 10.1016/j.jsb.2014.10.010. PMID:25448889 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ubiquitin protein ligase 3D structures

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