» Articles » PMID: 32251415

Crystal Structure of the SALL4-pomalidomide-cereblon-DDB1 Complex

Overview
Date 2020 Apr 7
PMID 32251415
Citations 35
Authors
Affiliations
Soon will be listed here.
Abstract

Thalidomide-dependent degradation of the embryonic transcription factor SALL4 by the CRL4 E3 ubiquitin ligase is a plausible major driver of thalidomide teratogenicity. The structure of the second zinc finger of SALL4 in complex with pomalidomide, cereblon and DDB1 reveals the molecular details of recruitment. Sequence differences and a shifted binding position relative to Ikaros offer a path to the rational design of cereblon-binding drugs with reduced teratogenic risk.

Citing Articles

Unraveling the Engagement of Kinases to CRBN Through a Shared Structural Motif to Optimize PROTACs Efficacy.

Rosignoli S, Giordani S, Pacelli M, Guarguaglini G, Paiardini A Biomolecules. 2025; 15(2).

PMID: 40001507 PMC: 11852972. DOI: 10.3390/biom15020206.


Development of PROTACs targeting estrogen receptor: an emerging technique for combating endocrine resistance.

Peng R, Liu X, Chen C, Guo R, Min J RSC Med Chem. 2025; .

PMID: 39823043 PMC: 11734508. DOI: 10.1039/d4md00961d.


Design of a Cereblon construct for crystallographic and biophysical studies of protein degraders.

Kroupova A, Spiteri V, Rutter Z, Furihata H, Darren D, Ramachandran S Nat Commun. 2024; 15(1):8885.

PMID: 39406745 PMC: 11480361. DOI: 10.1038/s41467-024-52871-9.


Asymmetric Dirhodium-Catalyzed Modification of Immunomodulatory Imide Drugs and Their Biological Assessment.

Tracy W, Davies G, Jia L, Evans E, Sun Z, Buenviaje J ACS Med Chem Lett. 2024; 15(9):1575-1583.

PMID: 39291008 PMC: 11403733. DOI: 10.1021/acsmedchemlett.4c00297.


Molecular glues for protein-protein interactions: Progressing toward a new dream.

Konstantinidou M, Arkin M Cell Chem Biol. 2024; 31(6):1064-1088.

PMID: 38701786 PMC: 11193649. DOI: 10.1016/j.chembiol.2024.04.002.