Crystal structure of the SALL4–pomalidomide–cereblon–DDB1 complex
- 6 April 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Structural & Molecular Biology
- Vol. 27 (4), 319-322
- https://doi.org/10.1038/s41594-020-0405-9
Abstract
Thalidomide-dependent degradation of the embryonic transcription factor SALL4 by the CRL4CRBN 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.Keywords
This publication has 24 references indexed in Scilit:
- The Myeloma Drug Lenalidomide Promotes the Cereblon-Dependent Destruction of Ikaros ProteinsScience, 2014
- Lenalidomide Causes Selective Degradation of IKZF1 and IKZF3 in Multiple Myeloma CellsScience, 2014
- REFMAC5 for the refinement of macromolecular crystal structuresActa crystallographica. Section D, Structural biology, 2011
- Features and development of CootActa crystallographica. Section D, Structural biology, 2010
- Identification of a Primary Target of Thalidomide TeratogenicityScience, 2010
- Phasercrystallographic softwareJournal of Applied Crystallography, 2007
- Molecular architecture and assembly of the DDB1–CUL4A ubiquitin ligase machineryNature, 2006
- SALL4 deletions are a common cause of Okihiro and acro-renal-ocular syndromes and confirm haploinsufficiency as the pathogenic mechanismJournal of Medical Genetics, 2004
- Mutations in SALL4 in malformed Father and Daughter postulated previously due to reflect mutagenesis by thalidomideBirth Defects Research Part A: Clinical and Molecular Teratology, 2004
- VMD: Visual molecular dynamicsJournal of Molecular Graphics, 1996