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9GAO

Crystal structure of CRBNmidi in complex with 2-(4-(2,6-dioxopiperidin-3-yl)phenoxy)-N-methylacetamide

This is a non-PDB format compatible entry.
Summary for 9GAO
Entry DOI10.2210/pdb9gao/pdb
Related8RQ1 8RQ8 8RQA
DescriptorProtein cereblon, 2-[4-[(3~{R})-2,6-bis(oxidanylidene)piperidin-3-yl]phenoxy]-~{N}-methyl-ethanamide, ZINC ION, ... (4 entities in total)
Functional Keywordse3 ligase, protac, tpd, molecular glue, targeted protein degradation, ligase
Biological sourceHomo sapiens (human)
More
Total number of polymer chains2
Total formula weight75641.00
Authors
Rutter, Z.J.,Kroupova, A.,Zollman, D.,Ciulli, A. (deposition date: 2024-07-29, release date: 2024-10-02, Last modification date: 2024-10-30)
Primary citationKroupova, 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: 39406745
DOI: 10.1038/s41467-024-52871-9
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (1.95 Å)
Structure validation

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PDB entries from 2024-11-13

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