{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Furihata H"],"funding":["MEXT | Japan Society for the Promotion of Science"],"pagination":["4578"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7490372"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["11(1)"],"pubmed_abstract":["Thalidomide and its derivatives exert not only therapeutic effects as immunomodulatory drugs (IMiDs) but also adverse effects such as teratogenicity, which are due in part to different C2H2 zinc-finger (ZF) transcription factors, IKZF1 (or IKZF3) and SALL4, respectively. Here, we report the structural bases for the SALL4-specific proteasomal degradation induced by 5-hydroxythalidomide, a primary thalidomide metabolite generated by the enzymatic activity of cytochrome P450 isozymes, through the interaction with cereblon (CRBN). The crystal structure of the metabolite-mediated human SALL4-CRBN complex and mutagenesis studies elucidate the complex formation enhanced by the interaction between CRBN and an additional hydroxy group of (S)-5-hydroxythalidomide and the variation in the second resi"],"journal":["Nature communications"],"pubmed_title":["Structural bases of IMiD selectivity that emerges by 5-hydroxythalidomide."],"pmcid":["PMC7490372"],"funding_grant_id":["JP17J0844"],"pubmed_authors":["Miyakawa T","Furihata H","Miyauchi Y","Sawasaki T","Yamanaka S","Tanokura M","Asano A","Shibata N","Honda T"],"additional_accession":[]},"is_claimable":false,"name":"Structural bases of IMiD selectivity that emerges by 5-hydroxythalidomide.","description":"Thalidomide and its derivatives exert not only therapeutic effects as immunomodulatory drugs (IMiDs) but also adverse effects such as teratogenicity, which are due in part to different C2H2 zinc-finger (ZF) transcription factors, IKZF1 (or IKZF3) and SALL4, respectively. Here, we report the structural bases for the SALL4-specific proteasomal degradation induced by 5-hydroxythalidomide, a primary thalidomide metabolite generated by the enzymatic activity of cytochrome P450 isozymes, through the interaction with cereblon (CRBN). The crystal structure of the metabolite-mediated human SALL4-CRBN complex and mutagenesis studies elucidate the complex formation enhanced by the interaction between CRBN and an additional hydroxy group of (S)-5-hydroxythalidomide and the variation in the second resi","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Sep","modification":"2026-05-03T20:33:50.201Z","creation":"2020-10-08T07:16:45Z"},"accession":"S-EPMC7490372","cross_references":{"pubmed":["32929090"],"doi":["10.1038/s41467-020-18488-4"]}}