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Malic enzymes catalyze the oxidative decarboxylation of L-malate to pyruvate and CO 2 with the reduction of the NAD(P) + cofactor in the presence of divalent cations. We report the crystal structures at up to 2.1 A resolution of human mitochondrial NAD(P) + -dependent malic enzyme in different pentary complexes with the natural substrate malate or pyruvate, the dinucleotide...
The regulation of human mitochondrial NAD(P) + -dependent malic enzyme (m-NAD-ME) by ATP and fumarate may be crucial for the metabolism of glutamine for energy production in rapidly proliferating tissues and tumors. Here we report the crystal structure at 2.2 A resolution of m-NAD-ME in complex with ATP, Mn 2+ , tartronate, and fumarate. Our structural, kinetic, and mutagenesis...
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