7PJK
Cereblon isoform 4 from Magnetospirillum gryphiswaldense in complex with a benzotriazole analog of thalidomide
Summary for 7PJK
| Entry DOI | 10.2210/pdb7pjk/pdb |
| Descriptor | Cereblon isoform 4, ZINC ION, (3S)-3-(benzotriazol-2-yl)piperidine-2,6-dione, ... (4 entities in total) |
| Functional Keywords | signaling protein, thalidomide analogues |
| Biological source | Magnetospirillum gryphiswaldense MSR-1 |
| Total number of polymer chains | 3 |
| Total formula weight | 41767.40 |
| Authors | Heim, C.,Hartmann, M.D.,Maiwald, S. (deposition date: 2021-08-24, release date: 2022-03-16, Last modification date: 2024-01-31) |
| Primary citation | Krasavin, M.,Bubyrev, A.,Kazantsev, A.,Heim, C.,Maiwald, S.,Zhukovsky, D.,Dar'in, D.,Hartmann, M.D.,Bunev, A. Replacing the phthalimide core in thalidomide with benzotriazole. J Enzyme Inhib Med Chem, 37:527-530, 2022 Cited by PubMed Abstract: The advent of proteolysis-targeting chimaeras (PROTACs) mandates that new ligands for the recruitment of E3 ligases are discovered. The traditional immunomodulatory drugs (IMiDs) such as thalidomide and its analogues (all based on the phthalimide glutarimide core) bind to Cereblon, the substrate receptor of the CRL4A E3 ligase. We designed a thalidomide analogue in which the phthalimide moiety was replaced with benzotriazole, using an innovative synthesis strategy. Compared to thalidomide, the resulting "benzotriazolo thalidomide" has a similar binding mode, but improved properties, as revealed in crystallographic analyses, affinity assays and cell culture. PubMed: 35220840DOI: 10.1080/14756366.2021.2024525 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.99 Å) |
Structure validation
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