Taxonomic distribution of proteins containing Iso_dh domains

The tree below includes only several representative species and genera. The complete taxonomic breakdown of all proteins containing Iso_dh domains can be accessed here. Click the counts or percentage values to display the corresponding proteins.

NAD(+)-dependent isocitrate dehydrogenase. Cloning, nucleotide sequence, anddisruption of the IDH2 gene from Saccharomyces cerevisiae.

Cupp JR, McAlister-Henn L
J Biol Chem. 1991; 266: 22199-205

NAD(+)-dependent isocitrate dehydrogenase from Saccharomyces cerevisiae iscomposed of two nonidentical subunits, designated IDH1 (Mr approximately 40,000) and IDH2 (Mr approximately 39,000). We have isolated and characterized a yeastgenomic clone containing the IDH2 gene. The amino acid sequence deduced from the gene indicates that IDH2 is synthesized as a precursor of 369 amino acids (Mr39,694) and is processed upon mitochondrial import to yield a mature protein of354 amino acids (Mr 37,755). Amino acid sequence comparison between S. cerevisiaeIDH2 and S. cerevisiae NADP(+)-dependent isocitrate dehydrogenase shows nosignificant sequence identity, whereas comparison of IDH2 and Escherichia coliNADP(+)-dependent isocitrate dehydrogenase reveals a 33% sequence identity. Toconfirm the identity of the IDH2 gene and examine the relationship between IDH1and IDH2, the IDH2 gene was disrupted by genomic replacement in a haploid yeaststrain. The disruption strain expressed no detectable IDH2, as determined byWestern blot analysis, and was found to lack NAD(+)-dependent isocitratedehydrogenase activity, indicating that IDH2 is essential for a functionalenzyme. Overexpression of IDH2, however, did not result in increasedNAD(+)-dependent isocitrate dehydrogenase activity, suggesting that both IDH1 andIDH2 subunits are required for catalytic activity. The disruption strain wasunable to utilize acetate as a carbon source and exhibited a 2-fold slower growthrate than wild type strains on glycerol or lactate. This growth phenotype isconsistent with NAD(+)-dependent isocitrate dehydrogenase performing an essentialrole in the oxidative function of the citric acid cycle.

Structure of a bacterial enzyme regulated by phosphorylation, isocitratedehydrogenase.

Hurley JH, Thorsness PE, Ramalingam V, Helmers NH, Koshland DE Jr, Stroud RM
Proc Natl Acad Sci U S A. 1989; 86: 8635-9

The structure of isocitrate dehydrogenase [threo-DS-isocitrate: NADP+oxidoreductase (decarboxylating), EC 1.1.1.42] from Escherichia coli has beensolved and refined at 2.5 A resolution and is topologically different from thatof any other dehydrogenase. This enzyme, a dimer of identical 416-residuesubunits, is inactivated by phosphorylation at Ser-113, which lies at the edge ofan interdomain pocket that also contains many residues conserved betweenisocitrate dehydrogenase and isopropylmalate dehydrogenase. Isocitratedehydrogenase contains an unusual clasp-like domain in which both polypeptidechains in the dimer interlock. Based on the structure of isocitrate dehydrogenaseand conservation with isopropylmalate dehydrogenase, we suggest that the activesite lies in an interdomain pocket close to the phosphorylation site.