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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… Click to show full abstract
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.
Journal Title: Biochemical and biophysical research communications
Year Published: 2022
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