| http://purl.uniprot.org/citations/31686031 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/31686031 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/31686031 | http://www.w3.org/2000/01/rdf-schema#comment | "The investigational drugs E7820, indisulam and tasisulam (aryl-sulfonamides) promote the degradation of the splicing factor RBM39 in a proteasome-dependent mechanism. While the activity critically depends on the cullin RING ligase substrate receptor DCAF15, the molecular details remain elusive. Here we present the cryo-EM structure of the DDB1-DCAF15-DDA1 core ligase complex bound to RBM39 and E7820 at a resolution of 4.4 Å, together with crystal structures of engineered subcomplexes. We show that DCAF15 adopts a new fold stabilized by DDA1, and that extensive protein-protein contacts between the ligase and substrate mitigate low affinity interactions between aryl-sulfonamides and DCAF15. Our data demonstrate how aryl-sulfonamides neo-functionalize a shallow, non-conserved pocket on DCAF15 to selectively bind and degrade RBM39 and the closely related splicing factor RBM23 without the requirement for a high-affinity ligand, which has broad implications for the de novo discovery of molecular glue degraders."xsd:string |
| http://purl.uniprot.org/citations/31686031 | http://purl.org/dc/terms/identifier | "doi:10.1038/s41589-019-0378-3"xsd:string |
| http://purl.uniprot.org/citations/31686031 | http://purl.org/dc/terms/identifier | "doi:10.1038/s41589-019-0378-3"xsd:string |
| http://purl.uniprot.org/citations/31686031 | http://purl.uniprot.org/core/author | "Cai Q."xsd:string |
| http://purl.uniprot.org/citations/31686031 | http://purl.uniprot.org/core/author | "Cai Q."xsd:string |
| http://purl.uniprot.org/citations/31686031 | http://purl.uniprot.org/core/author | "Li Z."xsd:string |
| http://purl.uniprot.org/citations/31686031 | http://purl.uniprot.org/core/author | "Li Z."xsd:string |
| http://purl.uniprot.org/citations/31686031 | http://purl.uniprot.org/core/author | "Zhang T."xsd:string |
| http://purl.uniprot.org/citations/31686031 | http://purl.uniprot.org/core/author | "Zhang T."xsd:string |
| http://purl.uniprot.org/citations/31686031 | http://purl.uniprot.org/core/author | "Gray N.S."xsd:string |
| http://purl.uniprot.org/citations/31686031 | http://purl.uniprot.org/core/author | "Gray N.S."xsd:string |
| http://purl.uniprot.org/citations/31686031 | http://purl.uniprot.org/core/author | "Yoon H."xsd:string |
| http://purl.uniprot.org/citations/31686031 | http://purl.uniprot.org/core/author | "Yoon H."xsd:string |
| http://purl.uniprot.org/citations/31686031 | http://purl.uniprot.org/core/author | "Fischer E.S."xsd:string |
| http://purl.uniprot.org/citations/31686031 | http://purl.uniprot.org/core/author | "Fischer E.S."xsd:string |
| http://purl.uniprot.org/citations/31686031 | http://purl.uniprot.org/core/author | "Nowak R.P."xsd:string |
| http://purl.uniprot.org/citations/31686031 | http://purl.uniprot.org/core/author | "Nowak R.P."xsd:string |
| http://purl.uniprot.org/citations/31686031 | http://purl.uniprot.org/core/author | "Donovan K.A."xsd:string |
| http://purl.uniprot.org/citations/31686031 | http://purl.uniprot.org/core/author | "Donovan K.A."xsd:string |
| http://purl.uniprot.org/citations/31686031 | http://purl.uniprot.org/core/author | "Eleuteri N.A."xsd:string |
| http://purl.uniprot.org/citations/31686031 | http://purl.uniprot.org/core/author | "Eleuteri N.A."xsd:string |
| http://purl.uniprot.org/citations/31686031 | http://purl.uniprot.org/core/author | "Faust T.B."xsd:string |
| http://purl.uniprot.org/citations/31686031 | http://purl.uniprot.org/core/author | "Faust T.B."xsd:string |