InterPro domain: IPR024084

This entry represents a structural domain found in all types of isocitrate dehydrogenase, and in isopropylmalate dehydrogenase and tartrate dehydrogenase. The crystal structure of Escherichia coli isopropylmalate dehydrogenase has been described [ 1 ].

The isocitrate and isopropylmalate dehydrogenases family includes isocitrate dehydrogenase (IDH), 3-isopropylmalate dehydrogenase (IMDH) and tartrate dehydrogenase.

IDH is an important enzyme of carbohydrate metabolism which catalyses the oxidative decarboxylation of isocitrate into alpha-ketoglutarate [ 2 , 3 ]. IDH is either dependent on NAD ⁺ ( 1.1.1.41 ) or on NADP ⁺ ( 1.1.1.42 ). In eukaryotes there are at least three isozymes of IDH: two are located in the mitochondrial matrix (one NAD ⁺ -dependent, the other NADP ⁺ -dependent), while the third one (also NADP ⁺ -dependent) is cytoplasmic. In Escherichia coli, the activity of a NADP ⁺ -dependent form of the enzyme is controlled by the phosphorylation of a serine residue; the phosphorylated form of IDH is completely inactivated.

IMDH ( 1.1.1.85 ) catalyses the third step in the biosynthesis of leucine in bacteria and fungi, the oxidative decarboxylation of 3-isopropylmalate into 2-oxo-4-methylvalerate [ 4 , 5 ].

Tartrate dehydrogenase ( 1.1.1.93 ) shows strong homology to prokaryotic isopropylmalate dehydrogenases and, to a lesser extent, isocitrate dehydrogenase [ 6 ]. It catalyses the reduction of tartrate to oxaloglycolate [ 7 ].

1. Crystal structures of Escherichia coli and Salmonella typhimurium 3-isopropylmalate dehydrogenase and comparison with their thermophilic counterpart from Thermus thermophilus. J. Mol. Biol. 266, 1016-31
2. Structure of a bacterial enzyme regulated by phosphorylation, isocitrate dehydrogenase. Proc. Natl. Acad. Sci. U.S.A. 86, 8635-9
3. NAD(+)-dependent isocitrate dehydrogenase. Cloning, nucleotide sequence, and disruption of the IDH2 gene from Saccharomyces cerevisiae. J. Biol. Chem. 266, 22199-205
4. Three-dimensional structure of a highly thermostable enzyme, 3-isopropylmalate dehydrogenase of Thermus thermophilus at 2.2 A resolution. J. Mol. Biol. 222, 725-38
5. Modeling substrate binding in Thermus thermophilus isopropylmalate dehydrogenase. Protein Sci. 4, 84-92
6. Tartrate dehydrogenase, a new member of the family of metal-dependent decarboxylating R-hydroxyacid dehydrogenases. Arch. Biochem. Biophys. 313, 15-21