{"title":"AADC缺陷的CRISPR/Cas9敲除模型揭示了结构环3不稳定性是催化失败的关键驱动因素。","authors":"Sema Kalkan Uçar, Cem Yıldırım, Thomas Opladen","doi":"10.1111/febs.70204","DOIUrl":null,"url":null,"abstract":"<p><p>The CRISPR-Cas9 dopa decarboxylase (DDC) gene knockout SH-SY5Y model for aromatic L-amino acid decarboxylase (AADC) deficiency provides a valuable neuronal platform for functional and structural investigation of pathogenic variants. In their study, Bertoldi et al. successfully recapitulate the biochemical and metabolic hallmarks of AADC deficiency using the AADC catalytic variants R347Q and L353P. Their combined structural and cellular approach identifies loop3 dynamics as a critical determinant of enzymatic dysfunction. This model may pave the way for the development of precision therapies.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A CRISPR/Cas9 knockout model for AADC deficiency reveals structural loop3 instability as a key driver of catalytic failure.\",\"authors\":\"Sema Kalkan Uçar, Cem Yıldırım, Thomas Opladen\",\"doi\":\"10.1111/febs.70204\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The CRISPR-Cas9 dopa decarboxylase (DDC) gene knockout SH-SY5Y model for aromatic L-amino acid decarboxylase (AADC) deficiency provides a valuable neuronal platform for functional and structural investigation of pathogenic variants. In their study, Bertoldi et al. successfully recapitulate the biochemical and metabolic hallmarks of AADC deficiency using the AADC catalytic variants R347Q and L353P. Their combined structural and cellular approach identifies loop3 dynamics as a critical determinant of enzymatic dysfunction. This model may pave the way for the development of precision therapies.</p>\",\"PeriodicalId\":94226,\"journal\":{\"name\":\"The FEBS journal\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2025-07-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"The FEBS journal\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1111/febs.70204\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"The FEBS journal","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1111/febs.70204","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
A CRISPR/Cas9 knockout model for AADC deficiency reveals structural loop3 instability as a key driver of catalytic failure.
The CRISPR-Cas9 dopa decarboxylase (DDC) gene knockout SH-SY5Y model for aromatic L-amino acid decarboxylase (AADC) deficiency provides a valuable neuronal platform for functional and structural investigation of pathogenic variants. In their study, Bertoldi et al. successfully recapitulate the biochemical and metabolic hallmarks of AADC deficiency using the AADC catalytic variants R347Q and L353P. Their combined structural and cellular approach identifies loop3 dynamics as a critical determinant of enzymatic dysfunction. This model may pave the way for the development of precision therapies.
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