8RQ9
Crystal structure of PROTAC CFT-1297 in complex with CRBN-midi and BRD4(BD2)
This is a non-PDB format compatible entry.
Summary for 8RQ9
| Entry DOI | 10.2210/pdb8rq9/pdb |
| Related | 8RQ1 8RQ8 8RQA 8RQC |
| Descriptor | Protein cereblon, Bromodomain-containing protein 4, (3~{S})-3-[7-[1-[7-[4-[6-(4-chlorophenyl)-1-methyl-spiro[[1,2,4]triazolo[4,3-a][1,4]benzodiazepine-4,1'-cyclopropane]-8-yl]pyrazol-1-yl]heptyl]piperidin-4-yl]-3-oxidanylidene-1~{H}-isoindol-2-yl]piperidine-2,6-dione, ... (5 entities in total) |
| Functional Keywords | e3 ligase, protac, tpd, targeted protein degradation, ligase |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 106857.91 |
| Authors | Darren, D.,Ramachandran, S.,Kroupova, A.,Zollman, D.,Ciulli, A. (deposition date: 2024-01-17, release date: 2024-09-25, Last modification date: 2024-10-30) |
| Primary citation | Kroupova, A.,Spiteri, V.A.,Rutter, Z.J.,Furihata, H.,Darren, D.,Ramachandran, S.,Chakraborti, S.,Haubrich, K.,Pethe, J.,Gonzales, D.,Wijaya, A.J.,Rodriguez-Rios, M.,Sturbaut, M.,Lynch, D.M.,Farnaby, W.,Nakasone, M.A.,Zollman, D.,Ciulli, A. Design of a Cereblon construct for crystallographic and biophysical studies of protein degraders. Nat Commun, 15:8885-8885, 2024 Cited by PubMed Abstract: The ubiquitin E3 ligase cereblon (CRBN) is the target of therapeutic drugs thalidomide and lenalidomide and is recruited by most targeted protein degraders (PROTACs and molecular glues) in clinical development. Biophysical and structural investigation of CRBN has been limited by current constructs that either require co-expression with the adaptor DDB1 or inadequately represent full-length protein, with high-resolution structures of degrader ternary complexes remaining rare. We present the design of CRBN, a construct that readily expresses from E. coli with high yields as soluble, stable protein without DDB1. We benchmark CRBN for wild-type functionality through a suite of biophysical techniques and solve high-resolution co-crystal structures of its binary and ternary complexes with degraders. We qualify CRBN as an enabling tool to accelerate structure-based discovery of the next generation of CRBN based therapeutics. PubMed: 39406745DOI: 10.1038/s41467-024-52871-9 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.91 Å) |
Structure validation
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