Fig. 5: Quaternary complex of CK1α + CRBN∆1-40 + DDB1∆BPB + SJ3149. | Nature Communications

Fig. 5: Quaternary complex of CK1α + CRBN∆1-40 + DDB1∆BPB + SJ3149.

From: Selective CK1α degraders exert antiproliferative activity against a broad range of human cancer cell lines

Fig. 5: Quaternary complex of CK1α + CRBN∆1-40 + DDB1∆BPB + SJ3149.

a Quaternary complex of CK1α (purple), CRBN (green), and DDB1 (blue) in the presence of molecular glue SJ3149 (shown as cyan sticks). b The magnified region of the binding interface of CK1α and CRBN that accommodates SJ3149 with hydrogen bonds is shown as dashed lines. c Surface representation of the SJ3149 binding pocket with the benzisoxazol exposed to bulk solvent and available for chemical modification. d The Fo–Fc electron density map (rendered at 2.5 sigma) of the ligand allows the unambiguous placement of SJ3149 in the binding site with the benzisoxazol moiety extending to directly H-bond with K18 of CK1α, and H353 and E377 of CRBN. Overlay of the lenalidomide quaternary complex (5FQD; lenalidomide shown as thin gray sticks) shows similar accommodation of the shared glutarimide moiety and the displacement of a water molecule (gray sphere) that was observed in the lenalidomide-bound complex upon SJ3149 binding.

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