5oha

Cereblon isoform 4 from Magnetospirillum gryphiswaldense in complex with 2-ThiohydantoinCereblon isoform 4 from Magnetospirillum gryphiswaldense in complex with 2-Thiohydantoin

Structural highlights 5oha is a 3 chain structure with sequence from Magnetospirillum gryphiswaldense. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.55Å Ligands: , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A4TVL0_9PROT Publication Abstract from PubMed The protein cereblon serves as a substrate receptor of a ubiquitin ligase complex that can be tuned toward different target proteins by cereblon-binding agents. This approach to targeted protein degradation is exploited in different clinical settings and has sparked the development of a growing number of thalidomide derivatives. Here, we probe the chemical space of cereblon binding beyond such derivatives and work out a simple set of chemical requirements, delineating the metaclass of cereblon effectors. We report co-crystal structures for a diverse set of compounds, including commonly used pharmaceuticals, but also find that already minimalistic cereblon-binding moieties might exert teratogenic effects in zebrafish. Our results may guide the design of a post-thalidomide generation of therapeutic cereblon effectors and provide a framework for the circumvention of unintended cereblon binding by negative design for future pharmaceuticals. Chemical Ligand Space of Cereblon.,Boichenko I, Bar K, Deiss S, Heim C, Albrecht R, Lupas AN, Hernandez Alvarez B, Hartmann MD ACS Omega. 2018 Sep 14;3(9):11163-11171. doi: 10.1021/acsomega.8b00959. , eCollection 2018 Sep 30. PMID:31459225 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

spinqualitylabelsall models 5oha, resolution 1.55Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image