Structural basis for the activity and regulation of human α-ketoglutarate dehydrogenase revealed by Cryo-EM
Structural basis for the activity and regulation of human α-ketoglutarate dehydrogenase revealed by Cryo-EM
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冷冻电镜揭示人类α-酮戊二酸脱氢酶活性和调节的结构基础
DOI：
10.1016/j.bbrc.2022.02.093
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发表时间：
2022
影响因子：
3.1
通讯作者：
Xiang Yu
中科院分区：
文献类型：
--
作者：
Youhuan Zhong;Yuanzhu Gao;Dejian Zhou;Xiaomin Ma;Huan Chen;Yingjie Xu;Wen Yang;Xiang Yu
人线粒体α-酮戊二酸（α-KG）脱氢酶复合物（hKGDHc）是一种经过充分研究的大分子酶，可将α-KG转化为琥珀酰辅酶A和NADH。该复合物的缺失导致几种疾病，包括神经退行性疾病。尽管其在人类代谢和疾病中的重要性，但hKGDHc的结构信息并不明确。在这里，我们报告的2.92 μ m分辨率冷冻电子显微镜（EM）结构的E1组件2-酮戊二酸脱氢酶（OGDH）。密度图包含残基129- 1，023，其几乎是OGDH的全长。结构清楚地显示了OGDH的活性位点和Ca 2+结合位点。这些结构信息将提高我们对hKGDHc的结构和功能的理解，并有利于靶向这种酶复合物的药物和基础科学。
The human mitochondrial alpha-ketoglutarate (α-KG) dehydrogenase complex (hKGDHc) is a well-studied macromolecular enzyme that converts α-KG to succinyl-CoA and NADH. Abnormalities of the complex lead to several diseases, including neurodegenerative disorders. Despite its importance in human metabolism and diseases, structural information on hKGDHc is not well defined. Here, we report the 2.92 Å resolution cryo-electron microscopy (EM) structure of its E1 component 2-oxoglutarate dehydrogenase (OGDH). The density map comprised residues 129–1,023, which is nearly the full length of OGDH. The structure clearly shows the active site and Ca2+binding site of OGDH. This structural information will improve our understanding of the structure and function of hKGDHc and benefit pharmaceutical and basic science targeting this enzyme complex.