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Yet, approximately 10 percent of AS individuals harbor distinct point mutations in the maternal allele resulting in the expression of full\u2010length E6AP variants that frequently display compromised ligase activity. In a high\u2010throughput screen, we identified cyanocobalamin, a vitamin B12\u2010derivative, and several alloxazine derivatives as activators of the AS\u2010linked E6AP\u2010F583S variant. Furthermore, we show by cross\u2010linking coupled to mass spectrometry that cobalamins affect the structural dynamics of E6AP\u2010F583S and apply limited proteolysis coupled to mass spectrometry to obtain information about the regions of E6AP that are involved in, or are affected by binding cobalamins and alloxazine derivatives. Our data suggest that dietary supplementation with vitamin B12 can be beneficial for AS individuals.<\/jats:p>","DOI":"10.1002\/cbic.202400184","type":"journal-article","created":{"date-parts":[[2024,4,4]],"date-time":"2024-04-04T10:02:01Z","timestamp":1712224921000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Cobalamins Function as Allosteric Activators of an Angelman Syndrome\u2010Associated UBE3A\/E6AP Variant"],"prefix":"10.1002","volume":"25","author":[{"given":"Franziska","family":"M\u00fcller","sequence":"first","affiliation":[{"name":"Department of Biology Konstanz Research School Chemical Biology University of Konstanz  Universit\u00e4tsstr. 10 78457 Konstanz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmin","family":"Jansen","sequence":"additional","affiliation":[{"name":"Department of Biology Konstanz Research School Chemical Biology University of Konstanz  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