PROSITE documentation PDOC00389
Isocitrate 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 or on NADP+ (EC 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 (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 [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.


Technical section

PROSITE method (with tools and information) covered by this documentation:

IDH_IMDH, PS00470; Isocitrate and isopropylmalate dehydrogenases signature  (PATTERN)


1AuthorsHurley J.H. Thorsness P.E. Ramalingam V. Helmers N.H. Koshland D.E. Jr. Stroud R.M.
TitleStructure of a bacterial enzyme regulated by phosphorylation, isocitrate dehydrogenase.
SourceProc. Natl. Acad. Sci. U.S.A. 86:8635-8639(1989).
PubMed ID2682654

2AuthorsCupp J.R. McAlister-Henn L.
TitleNAD(+)-dependent isocitrate dehydrogenase. Cloning, nucleotide sequence, and disruption of the IDH2 gene from Saccharomyces cerevisiae.
SourceJ. Biol. Chem. 266:22199-22205(1991).
PubMed ID1939242

3AuthorsImada K. Sato M. Tanaka N. Katsube Y. Matsuura Y. Oshima T.
TitleThree-dimensional structure of a highly thermostable enzyme, 3-isopropylmalate dehydrogenase of Thermus thermophilus at 2.2 A resolution.
SourceJ. Mol. Biol. 222:725-738(1991).
PubMed ID1748999

4AuthorsZhang T. Koshland D.E. Jr.
TitleModeling substrate binding in Thermus thermophilus isopropylmalate dehydrogenase.
SourceProtein Sci. 4:84-92(1995).
PubMed ID7773180

5AuthorsTipton P.A. Beecher B.S.
TitleTartrate dehydrogenase, a new member of the family of metal-dependent decarboxylating R-hydroxyacid dehydrogenases.
SourceArch. Biochem. Biophys. 313:15-21(1994).
PubMed ID8053675

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