Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Molecular glue CELMoD compounds are regulators of cereblon conformation.
Journal, issue, pages	Science, Vol. 378, Issue 6619, Page 549-553, Year 2022
Publish date	Nov 4, 2022
Authors	Edmond R Watson / Scott Novick / Mary E Matyskiela / Philip P Chamberlain / Andres H de la Peña / Jinyi Zhu / Eileen Tran / Patrick R Griffin / Ingrid E Wertz / Gabriel C Lander /
PubMed Abstract	Cereblon (CRBN) is a ubiquitin ligase (E3) substrate receptor protein co-opted by CRBN E3 ligase modulatory drug (CELMoD) agents that target therapeutically relevant proteins for degradation. Prior ...Cereblon (CRBN) is a ubiquitin ligase (E3) substrate receptor protein co-opted by CRBN E3 ligase modulatory drug (CELMoD) agents that target therapeutically relevant proteins for degradation. Prior crystallographic studies defined the drug-binding site within CRBN's thalidomide-binding domain (TBD), but the allostery of drug-induced neosubstrate binding remains unclear. We performed cryo-electron microscopy analyses of the DNA damage-binding protein 1 (DDB1)-CRBN apo complex and compared these structures with DDB1-CRBN in the presence of CELMoD compounds alone and complexed with neosubstrates. Association of CELMoD compounds to the TBD is necessary and sufficient for triggering CRBN allosteric rearrangement from an open conformation to the canonical closed conformation. The neosubstrate Ikaros only stably associates with the closed CRBN conformation, illustrating the importance of allostery for CELMoD compound efficacy and informing structure-guided design strategies to improve therapeutic efficacy.
External links	Science / PubMed:36378961 / PubMed Central
Methods	EM (single particle)
Resolution	3.1 - 3.9 Å
Structure data	27012 8cvp EMDB-27012, PDB-8cvp: Cereblon-DDB1 in the Apo form Method: EM (single particle) / Resolution: 3.4 Å 27234 8d7u EMDB-27234, PDB-8d7u: Cereblon~DDB1 bound to CC-92480 with DDB1 in the linear conformation Method: EM (single particle) / Resolution: 3.1 Å 27235 8d7v EMDB-27235, PDB-8d7v: Cereblon~DDB1 bound to CC-92480 with DDB1 in the twisted conformation Method: EM (single particle) / Resolution: 3.2 Å 27236 8d7w EMDB-27236, PDB-8d7w: Cereblon~DDB1 bound to CC-92480 with DDB1 in the hinged conformation Method: EM (single particle) / Resolution: 3.1 Å 27237 8d7x EMDB-27237, PDB-8d7x: Cereblon~DDB1 in the Apo form with DDB1 in the hinged conformation Method: EM (single particle) / Resolution: 3.4 Å 27238 8d7y EMDB-27238, PDB-8d7y: Cereblon-DDB1 in the Apo form with DDB1 in the twisted conformation Method: EM (single particle) / Resolution: 3.4 Å EMDB-27239: Cereblon bound to CC-92480, Focused Refinement Method: EM (single particle) / Resolution: 3.1 Å 27240 8d7z EMDB-27240, PDB-8d7z: Cereblon-DDB1 bound to CC-92480 and Ikaros ZF1-2-3 Method: EM (single particle) / Resolution: 3.1 Å 27241 8d80 EMDB-27241, PDB-8d80: Cereblon~DDB1 bound to Iberdomide and Ikaros ZF1-2-3 Method: EM (single particle) / Resolution: 3.6 Å 27242 8d81 EMDB-27242, PDB-8d81: Cereblon~DDB1 bound to Pomalidomide Method: EM (single particle) / Resolution: 3.9 Å
Chemicals	ChemComp-ZN: Unknown entry ChemComp-QFC: Mezigdomide ChemComp-8W7: (3S)-3-[4-({4-[(morpholin-4-yl)methyl]phenyl}methoxy)-1-oxo-1,3-dihydro-2H-isoindol-2-yl]piperidine-2,6-dione ChemComp-Y70: S-Pomalidomide
Source	homo sapiens (human)
Keywords	LIGASE / Ubiquitin / CRL4 / Adaptor / Cereblon / E3