中山醫學大學機構典藏 CSMUIR:Item 310902500/23413
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    题名: Single nucleotide variants lead to dysregulation of the human mitochondrial NAD(P)(+)-dependent malic enzyme
    作者: Hsieh, JY;Yang, HP;Tewary, SK;Cheng, HC;Liu, YL;Tai, SC;Chen, WL;Hsu, CH;Huang, TJ;Chou, CJ;Huang, YN;Peng, CT;Ho, MC;Liu, GY;Hung, HC
    日期: 2021
    上传时间: 2022-08-05T09:36:53Z (UTC)
    出版者: CELL PRESS
    摘要: Human mitochondrial NAD(P)(+)-dependent malic enzyme (ME2) is well recognized to associate with cancer cell metabolism, and the single nucleotide variants (SNVs) of ME2 may play a role in enzyme regulation. Here we reported that the SNVs of ME2 occurring in the allosteric sites lead to inactivation or overactivation of ME2. TwoME2-SNVs, ME2_R67Q and ME2-R484W, that demonstrated inactivating or overactivating enzyme activities of ME2, respectively, have different impact toward the cells. The cells with overactivating SNV enzyme, ME2_R484W, grow more rapidly and are more resistant to cellular senescence than the cells with wild-type or inactivating SNV enzyme, ME2_R67Q. Crystal structures of these two ME2-SNVs reveal that ME2_R67Q was an inactivating dead form,'' and ME2_R484W was an overactivating closed form'' of the enzyme. The resolved ME2-SNV structures provide a molecular basis to explain the abnormal kinetic properties of these SNV enzymes.
    URI: http://dx.doi.org/10.1016/j.isci.2021.102034
    https://www.webofscience.com/wos/woscc/full-record/WOS:000621266700009
    https://ir.csmu.edu.tw:8080/handle/310902500/23413
    關聯: ISCIENCE ,2021,v24,issue 2
    显示于类别:[中山醫學大學研究成果] 期刊論文

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