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https://ir.csmu.edu.tw:8080/ir/handle/310902500/23413
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Title: | Single nucleotide variants lead to dysregulation of the human mitochondrial NAD(P)(+)-dependent malic enzyme |
Authors: | 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 |
Date: | 2021 |
Issue Date: | 2022-08-05T09:36:53Z (UTC)
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Publisher: | CELL PRESS |
Abstract: | 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 |
Relation: | ISCIENCE ,2021,v24,issue 2 |
Appears in Collections: | [中山醫學大學研究成果] 期刊論文
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