哺乳动物 NAD 依赖性异柠檬酸脱氢酶催化和调节的分子见解。
Molecular insights into the catalysis and regulation of mammalian NAD-dependent isocitrate dehydrogenases.
机构信息
State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China; School of Life Science and Technology, ShanghaiTech University, 393 Huaxia Zhong Road, Shanghai 201210, China.
出版信息
Curr Opin Struct Biol. 2023 Oct;82:102672. doi: 10.1016/j.sbi.2023.102672. Epub 2023 Aug 3.
Eukaryotic NAD-dependent isocitrate dehydrogenases (NAD-IDHs) are mitochondria-localized enzymes which catalyze the oxidative decarboxylation of isocitrate to α-ketoglutarate using NAD as a cofactor. In mammals, NAD-IDHs (or IDH3) consist of three types of subunits (α, β, and γ), and exist as (αβγ) heterooctamer. Mammalian NAD-IDHs are regulated allosterically and/or competitively by a diversity of metabolites including citrate, ADP, ATP, NADH, and NADPH, which are associated with cellular metabolite flux, energy demands, and redox status. Proper assembly of the component subunits is essential for the catalysis and regulation of the enzymes. Recently, crystal structures of human IDH3 have been solved in apo form and in complex with various ligands, revealing the molecular mechanisms for the assembly, catalysis, and regulation of the enzyme.
真核生物 NAD 依赖性异柠檬酸脱氢酶（NAD-IDHs）是定位于线粒体的酶，它利用 NAD 作为辅助因子催化异柠檬酸的氧化脱羧生成 α-酮戊二酸。在哺乳动物中，NAD-IDHs（或 IDH3）由三种类型的亚基（α、β 和 γ）组成，并且以（αβγ）异源八聚体的形式存在。哺乳动物 NAD-IDHs 受到多种代谢物的变构和/或竞争性调节，包括柠檬酸、ADP、ATP、NADH 和 NADPH，这些代谢物与细胞代谢通量、能量需求和氧化还原状态有关。组件亚基的正确组装对于酶的催化和调节是必不可少的。最近，已解析出人 IDH3 的apo 形式和与各种配体结合的晶体结构，揭示了该酶组装、催化和调节的分子机制。
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