7pso

Cereblon isoform 4 from Magnetospirillum gryphiswaldense in complex with Avadomide (CC-122)

spinqualitylabelsall models 7pso, resolution 1.52Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7pso 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 1.52Å Ligands: 835, EF2, PO4, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A4TVL0_9PROT Publication Abstract from PubMed Cereblon (CRBN) is the substrate receptor of the CRL4(CRBN) E3 ubiquitin ligase and is a central player in targeted protein degradation. It is the target of the thalidomide-derived immunomodulatory drugs (IMiDs) and is one of the most widely employed receptors for proteolysis-targeting chimeras (PROTACs), both of which induce the ubiquitination and subsequent proteasomal degradation of target proteins. Structural studies of ligand binding to CRBN are crucial to elucidate the mechanisms of action and for mediation of side effects, ultimately aiding the development of next-generation IMiDs and PROTACs. With this aim, a crystal-soaking system based on the single-domain bacterial homologue MsCI4 has previously been established and used to delineate the binding modes of several classes of small molecules, including FDA-approved drugs, at the molecular level. Here, this system was used to characterize the binding of the next-generation IMiDs avadomide (CC-122) and iberdomide (CC-220) at high resolution, highlighting the advantages and limitations of the MsCI4 system and its implications for the development of future cereblon effectors. High-resolution structures of the bound effectors avadomide (CC-122) and iberdomide (CC-220) highlight advantages and limitations of the MsCI4 soaking system.,Heim C, Hartmann MD Acta Crystallogr D Struct Biol. 2022 Mar 1;78(Pt 3):290-298. doi:, 10.1107/S2059798322000092. Epub 2022 Feb 18. PMID:35234143 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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