InterPro domain: IPR004434

Several NAD- or NADP-dependent dehydrogenases, including 3-isopropylmalate dehydrogenase, tartrate dehydrogenase, and the multimeric forms of isocitrate dehydrogenase, share a nucleotide binding domain unrelated to that of lactate dehydrogenase and its homologues. These enzymes dehydrogenate their substates at a H-C-OH site adjacent to a H-C-COOH site; the latter carbon, now adjacent to a carbonyl group, readily decarboxylates.

Mitochondrial NAD-dependent isocitrate dehydrogenases (IDH) resemble prokaryotic NADP-dependent IDH and 3-isopropylmalate dehydrogenase (an NAD-dependent enzyme) more closely than they resemble eukaryotic NADP-dependent IDH. The mitochondrial NAD-dependent isocitrate dehydrogenase is believed to be an alpha(2)-beta-gamma heterotetramer. All subunits are homologous and belog to this group.

The NADP-dependent IDH of Thermus thermophilus strain HB8 resembles these NAD-dependent IDH, except for the residues involved in cofactor specificity, much more closely than it resembles other prokaryotic NADP-dependent IDH, including that of Thermus aquaticus.