PROSITE documentation PDOC00389Isocitrate and isopropylmalate dehydrogenases signature
Isocitrate dehydrogenase (IDH) [1,2] is an important enzyme of carbohydrate metabolism which catalyzes the oxidative decarboxylation of isocitrate into α-ketoglutarate. IDH is either dependent on NAD+ (EC 1.1.1.41) or on NADP+ (EC 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.
3-isopropylmalate dehydrogenase (EC 1.1.1.85) (IMDH) [3,4] catalyzes the third step in the biosynthesis of leucine in bacteria and fungi, the oxidative decarboxylation of 3-isopropylmalate into 2-oxo-4-methylvalerate.
Tartrate dehydrogenase (EC 1.1.1.93) [5] catalyzes the reduction of tartrate to oxaloglycolate.
These enzymes are evolutionary related [1,3,4,5]. The best conserved region of these enzymes is a glycine-rich stretch of residues located in the C-terminal section. We have used this region as a signature pattern.
Last update:December 2004 / Pattern and text revised.
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PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Hurley J.H. Thorsness P.E. Ramalingam V. Helmers N.H. Koshland D.E. Jr. Stroud R.M. |
| Title | Structure of a bacterial enzyme regulated by phosphorylation, isocitrate dehydrogenase. | |
| Source | Proc. Natl. Acad. Sci. U.S.A. 86:8635-8639(1989). | |
| PubMed ID | 2682654 |
| 2 | Authors | Cupp J.R. McAlister-Henn L. |
| Title | NAD(+)-dependent isocitrate dehydrogenase. Cloning, nucleotide sequence, and disruption of the IDH2 gene from Saccharomyces cerevisiae. | |
| Source | J. Biol. Chem. 266:22199-22205(1991). | |
| PubMed ID | 1939242 |
| 3 | Authors | Imada K. Sato M. Tanaka N. Katsube Y. Matsuura Y. Oshima T. |
| Title | Three-dimensional structure of a highly thermostable enzyme, 3-isopropylmalate dehydrogenase of Thermus thermophilus at 2.2 A resolution. | |
| Source | J. Mol. Biol. 222:725-738(1991). | |
| PubMed ID | 1748999 |
| 4 | Authors | Zhang T. Koshland D.E. Jr. |
| Title | Modeling substrate binding in Thermus thermophilus isopropylmalate dehydrogenase. | |
| Source | Protein Sci. 4:84-92(1995). | |
| PubMed ID | 7773180 |
| 5 | Authors | Tipton P.A. Beecher B.S. |
| Title | Tartrate dehydrogenase, a new member of the family of metal-dependent decarboxylating R-hydroxyacid dehydrogenases. | |
| Source | Arch. Biochem. Biophys. 313:15-21(1994). | |
| PubMed ID | 8053675 |
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