A CRISPR/Cas9 knockout model for AADC deficiency reveals structural loop3 instability as a key driver of catalytic failure.

Sema Kalkan Uçar, Cem Yıldırım, Thomas Opladen
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Abstract

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.

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。
芳香l -氨基酸脱羧酶(AADC)缺陷的CRISPR-Cas9多巴脱羧酶(DDC)基因敲除SH-SY5Y模型为致病变异的功能和结构研究提供了有价值的神经元平台。在他们的研究中,Bertoldi等人利用AADC催化变体R347Q和L353P成功概括了AADC缺乏症的生化和代谢特征。他们结合结构和细胞方法确定了环3动力学是酶功能障碍的关键决定因素。这种模式可能为精确治疗的发展铺平道路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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