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258  structures 5707  species 1  interaction 12354  sequences 30  architectures

Family: Iso_dh (PF00180)

Summary: Isocitrate/isopropylmalate dehydrogenase

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This is the Wikipedia entry entitled "Isocitrate/isopropylmalate dehydrogenase family". More...

Isocitrate/isopropylmalate dehydrogenase family Edit Wikipedia article

Isocitrate/isopropylmalate dehydrogenase
PDB 1cw4 EBI.jpg
crystal structure of k230m isocitrate dehydrogenase in complex with alpha-ketoglutarate
Identifiers
Symbol Iso_dh
Pfam PF00180
Pfam clan CL0270
InterPro IPR001804
PROSITE PDOC00389
SCOP 1hex
SUPERFAMILY 1hex

In molecular biology, the isocitrate/isopropylmalate dehydrogenase family is a protein family consisting of the evolutionary related enzymes isocitrate dehydrogenase, 3-isopropylmalate dehydrogenase and tartrate dehydrogenase.[1][2][3][4]

Isocitrate dehydrogenase (IDH), is an important enzyme of carbohydrate metabolism which catalyses the oxidative decarboxylation of isocitrate into alpha-ketoglutarate.[1][5] 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) catalyses the third step in the biosynthesis of leucine in bacteria and fungi, the oxidative decarboxylation of 3-isopropylmalate into 2-oxo-4-methylvalerate.[2][3]

Tartrate dehydrogenase EC 1.1.1.93 catalyses the reduction of tartrate to oxaloglycolate.[4]

References[edit]

  1. ^ a b Hurley JH, Thorsness PE, Ramalingam V, Helmers NH, Koshland DE, Stroud RM (November 1989). "Structure of a bacterial enzyme regulated by phosphorylation, isocitrate dehydrogenase". Proc. Natl. Acad. Sci. U.S.A. 86 (22): 8635–9. doi:10.1073/pnas.86.22.8635. PMC 298342. PMID 2682654. 
  2. ^ a b Imada K, Sato M, Tanaka N, Katsube Y, Matsuura Y, Oshima T (December 1991). "Three-dimensional structure of a highly thermostable enzyme, 3-isopropylmalate dehydrogenase of Thermus thermophilus at 2.2 A resolution". J. Mol. Biol. 222 (3): 725–38. doi:10.1016/0022-2836(91)90508-4. PMID 1748999. 
  3. ^ a b Zhang T, Koshland DE (January 1995). "Modeling substrate binding in Thermus thermophilus isopropylmalate dehydrogenase". Protein Sci. 4 (1): 84–92. doi:10.1002/pro.5560040111. PMC 2142962. PMID 7773180. 
  4. ^ a b Tipton PA, Beecher BS (August 1994). "Tartrate dehydrogenase, a new member of the family of metal-dependent decarboxylating R-hydroxyacid dehydrogenases". Arch. Biochem. Biophys. 313 (1): 15–21. doi:10.1006/abbi.1994.1352. PMID 8053675. 
  5. ^ Cupp JR, McAlister-Henn L (November 1991). "NAD(+)-dependent isocitrate dehydrogenase. Cloning, nucleotide sequence, and disruption of the IDH2 gene from Saccharomyces cerevisiae". J. Biol. Chem. 266 (33): 22199–205. PMID 1939242. 

This article incorporates text from the public domain Pfam and InterPro IPR001804

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Isocitrate/isopropylmalate dehydrogenase Provide feedback

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External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR024084

Isocitrate dehydrogenase (IDH) [PUBMED:2682654, PUBMED:1939242] is an important enzyme of carbohydrate metabolism which catalyses the oxidative decarboxylation of isocitrate into alpha-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) [PUBMED:1748999, PUBMED:7773180] catalyses 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) [PUBMED:8053675] catalyses the reduction of tartrate to oxaloglycolate.

These enzymes are evolutionary related. To this family also belongs the enzyme tartrate dehydrogenase, which shows strong homology to prokaryotic isopropylmalate dehydrogenases and, to a lesser extent, isocitrate dehydrogenase [PUBMED:8053675].

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 [PUBMED:9086278].

Gene Ontology

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Domain organisation

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Pfam Clan

This family is a member of clan Iso_DH (CL0270), which has the following description:

This superfamily of enzymes form dimers and have an active site between the two halves.

The clan contains the following 5 members:

FA_synthesis IDH Iso_dh PdxA PTA_PTB

Alignments

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(7894)
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(2017)
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  Seed
(23)
Full
(12354)
Representative proteomes NCBI
(9844)
Meta
(7894)
RP15
(1065)
RP35
(2017)
RP55
(2773)
RP75
(3358)
Alignment:
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  Seed
(23)
Full
(12354)
Representative proteomes NCBI
(9844)
Meta
(7894)
RP15
(1065)
RP35
(2017)
RP55
(2773)
RP75
(3358)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

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Pfam alignments:

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Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Prosite
Previous IDs: isodh;
Type: Domain
Author: Finn RD
Number in seed: 23
Number in full: 12354
Average length of the domain: 320.30 aa
Average identity of full alignment: 29 %
Average coverage of the sequence by the domain: 93.82 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.1 20.1
Trusted cut-off 20.1 20.2
Noise cut-off 20.0 20.0
Model length: 348
Family (HMM) version: 15
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Species distribution

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Interactions

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Iso_dh

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Iso_dh domain has been found. There are 258 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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