Structural highlights
Publication Abstract from PubMed
Thalidomide-dependent degradation of the embryonic transcription factor SALL4 by the CRL4(CRBN) 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.
Crystal structure of the SALL4-pomalidomide-cereblon-DDB1 complex.,Matyskiela ME, Clayton T, Zheng X, Mayne C, Tran E, Carpenter A, Pagarigan B, McDonald J, Rolfe M, Hamann LG, Lu G, Chamberlain PP Nat Struct Mol Biol. 2020 Apr;27(4):319-322. doi: 10.1038/s41594-020-0405-9. Epub, 2020 Apr 6. PMID:32251415[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Matyskiela ME, Clayton T, Zheng X, Mayne C, Tran E, Carpenter A, Pagarigan B, McDonald J, Rolfe M, Hamann LG, Lu G, Chamberlain PP. Crystal structure of the SALL4-pomalidomide-cereblon-DDB1 complex. Nat Struct Mol Biol. 2020 Apr;27(4):319-322. doi: 10.1038/s41594-020-0405-9. Epub, 2020 Apr 6. PMID:32251415 doi:http://dx.doi.org/10.1038/s41594-020-0405-9
