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Literature summary for 1.1.1.41 extracted from
- Each conserved active site tyr in the three subunits of human isocitrate dehydrogenase has a different function (2010), J. Biol. Chem., 285, 20520-20525.
Activating Compound
| Activating Compound | Comment | Organism | Structure |
|---|---|---|---|
| ADP | allosteric activation by ADP involving residue betaY126. In the presence of 1 mM ADP, the Km,isocitrate is reduced almost equally in the wild-type, 3.6fold, and the alphaY126E mutant, 4.3fold | Homo sapiens |  |
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| expression of wild-type and mutant NAD-IDHs in Escherichia coli | Homo sapiens |
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| alphaY126E | site-directed mutagenesis of subunit alpha, almost inactive mutant, shows low activity at pH 6.1 instead of pH 7.2, Km,Mn2+ is 30fold higher in the alphaY126E mutant as compared with the wild-type. Km,NAD+ for the alphaY126E mutant is 29fold higher than that of the wild-type. The Vmax of the wild-type at pH 6.1 is 0.0144 mmol/min/mg, whereas that for the alphaY126E mutant is only 0.00103 mmol/min/mg, suggesting a critical role for the residue in enzyme activity | Homo sapiens |
| alphaY126F | site-directed mutagenesis of subunit alpha, inactive mutant | Homo sapiens |
| alphaY126S | site-directed mutagenesis of subunit alpha, inactive mutant | Homo sapiens |
| betaY137E | site-directed mutagenesis of subunit beta, the mutant shows reduced activity compared to the wild-type enzyme | Homo sapiens |
| betaY137F | site-directed mutagenesis of subunit beta, the mutant shows reduced activity compared to the wild-type enzyme | Homo sapiens |
| betaY137S | site-directed mutagenesis of subunit beta, the mutant shows reduced activity compared to the wild-type enzyme | Homo sapiens |
| gammaY135F | site-directed mutagenesis of subunit gamma, inactive mutant | Homo sapiens |
KM Value [mM]
| KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| 0.06 | - |
NAD+ | pH 7.2, 25°C, recombinant wild-type enzyme | Homo sapiens | |
| 0.09 | - |
NAD+ | pH 7.2, 25°C, recombinant mutant betaY137E | Homo sapiens | |
| 0.09 | - |
isocitrate | pH 7.2, 25°C, recombinant mutant betaY137E, in presence of 1 mM ADP | Homo sapiens | |
| 0.12 | - |
NAD+ | pH 7.2, 25°C, recombinant mutant betaY137F | Homo sapiens | |
| 0.28 | - |
isocitrate | pH 7.2, 25°C, recombinant mutant betaY137F, in presence of 1 mM ADP | Homo sapiens | |
| 0.5 | - |
isocitrate | pH 7.2, 25°C, recombinant wild-type enzyme, in presence of 1 mM ADP | Homo sapiens | |
| 0.63 | - |
NAD+ | pH 7.2, 25°C, recombinant mutant betaY137S | Homo sapiens | |
| 0.92 | - |
isocitrate | pH 7.2, 25°C, recombinant mutant betaY137S, in presence of 1 mM ADP | Homo sapiens | |
| 1.2 | - |
isocitrate | pH 7.2, 25°C, recombinant mutant betaY137S | Homo sapiens | |
| 1.8 | - |
isocitrate | pH 7.2, 25°C, recombinant mutant betaY137F | Homo sapiens | |
| 2 | - |
isocitrate | pH 7.2, 25°C, recombinant wild-type enzyme | Homo sapiens | |
| 3.4 | - |
isocitrate | pH 7.2, 25°C, recombinant mutant betaY137E | Homo sapiens | |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| mitochondrion | - |
Homo sapiens | 5739 | - |
Metals/Ions
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| Mn2+ | activates, Km values for wild-type and betaY137 mutants are 0.11-0.18 mM | Homo sapiens | |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| isocitrate + NAD+ | Homo sapiens | - |
2-oxoglutarate + NADH + H+ + CO2 | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | - |
- |
- |
Purification (Commentary)
| Purification (Comment) | Organism |
|---|---|
| recombinant wild-type and mutant NAD-IDHs from Escherichia coli by ammonium sulfate fractionation, anion exchange chromatography, ultrafiltration, and gel filtration | Homo sapiens |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| isocitrate + NAD+ | - |
Homo sapiens | 2-oxoglutarate + NADH + H+ + CO2 | - |
? | |
| isocitrate + NAD+ | residue Y137 of subunit beta is involved in NAD+ binding and allosteric activation by ADP, residue Y126 of subunit alpha is required for catalytic activity and likely acts as a general acid in the reaction, gammaY135 is also required for catalytic activity and may be involved in proper folding of the enzyme. The corresponding tyrosines in the three dissimilar subunits of NAD-IDH thus have distinctive functions | Homo sapiens | 2-oxoglutarate + NADH + H+ + CO2 | - |
? | |
Subunits
| Subunits | Comment | Organism |
|---|---|---|
| heterotetramer | determination of secondary structure by circular dichroism, subunit molar ratio of wild-type and mutant NAD-IDHs, overview | Homo sapiens |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| isocitrate dehydrogenase | - |
Homo sapiens |
| NAD-IDH | - |
Homo sapiens |
Temperature Optimum [°C]
| Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
|---|---|---|---|
| 25 | - |
assay at | Homo sapiens |
pH Optimum
| pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
|---|---|---|---|
| 7.2 | - |
assay at | Homo sapiens |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| NAD+ | - |
Homo sapiens | |
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