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Literature summary for 1.8.1.4 extracted from
- Characterization of site-specific mutations in human dihydrolipoamide dehydrogenase significantly destabilizing the transition state of the enzyme catalysis (2015), J. Korean Chem. Soc., 59, 344-348 .
No PubMed abstract available
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| gene dld, recombinant expression of His-tagged wild-type and mutant enzymes in Escherichia coli strain XL-1 Blue | Homo sapiens |
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| C50A | site-directed mutagenesis, catalytic efficiency of mutant C50A toward NAD+ decreases 5317fold compared to the wild-type enzyme, the mutation destroys the active disulfide center between Cys45 and Cys50, which restricts the freedom of Cys50 | Homo sapiens |
| C50T | site-directed mutagenesis, catalytic efficiency of mutant C50A toward NAD+ decreases 2057fold compared to the wild-type enzyme, the mutation destroys the active disulfide center between Cys45 and Cys50, which restricts the freedom of Cys50 | Homo sapiens |
KM Value [mM]
| KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| 0.16 | - |
dihydrolipoamide | enzyme mutant C50T, pH 8.0, 37°C | Homo sapiens |  |
| 0.19 | - |
NAD+ | wild-type enzyme, pH 8.0, 37°C | Homo sapiens | |
| 0.2 | - |
NAD+ | enzyme mutant C50T, pH 8.0, 37°C | Homo sapiens | |
| 0.22 | - |
dihydrolipoamide | enzyme mutant C50A, pH 8.0, 37°C | Homo sapiens | |
| 0.47 | - |
NAD+ | enzyme mutant C50A, pH 8.0, 37°C | Homo sapiens | |
| 0.64 | - |
dihydrolipoamide | wild-type enzyme, pH 8.0, 37°C | Homo sapiens | |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| mitochondrion | - |
Homo sapiens | 5739 | - |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| dihydrolipoamide + NAD+ | Homo sapiens | - |
lipoamide + NADH + H+ | - |
r | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | P09622 | - |
- |
Purification (Commentary)
| Purification (Comment) | Organism |
|---|---|
| recombinant His-tagged wild-type and mutant enzymes from Escherichia coli strain XL-1 Blue by nickel affinity chromatography and dialysis | Homo sapiens |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| dihydrolipoamide + NAD+ | - |
Homo sapiens | lipoamide + NADH + H+ | - |
r | |
Subunits
| Subunits | Comment | Organism |
|---|---|---|
| homodimer | - |
Homo sapiens |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| dihydrolipoamide dehydrogenase | - |
Homo sapiens |
| dihydrolipoamide:NAD+ oxidoreductase | - |
Homo sapiens |
| E3 | - |
Homo sapiens |
Temperature Optimum [°C]
| Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
|---|---|---|---|
| 37 | - |
assay at | Homo sapiens |
Turnover Number [1/s]
| Turnover Number Minimum [1/s] | Turnover Number Maximum [1/s] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| 0.42 | - |
NAD+ | enzyme mutant C50A, pH 8.0, 37°C | Homo sapiens | |
| 0.42 | - |
dihydrolipoamide | enzyme mutant C50A, pH 8.0, 37°C | Homo sapiens | |
| 0.46 | - |
NAD+ | enzyme mutant C50T, pH 8.0, 37°C | Homo sapiens | |
| 0.46 | - |
dihydrolipoamide | enzyme mutant C50T, pH 8.0, 37°C | Homo sapiens | |
| 899 | - |
NAD+ | wild-type enzyme, pH 8.0, 37°C | Homo sapiens | |
| 899 | - |
dihydrolipoamide | wild-type enzyme, pH 8.0, 37°C | Homo sapiens | |
pH Optimum
| pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
|---|---|---|---|
| 8 | - |
assay at | Homo sapiens |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| FAD | one FAD as a prosthetic group at each subunit | Homo sapiens | |
| NAD+ | - |
Homo sapiens | |
| NADH | - |
Homo sapiens | |
General Information
| General Information | Comment | Organism |
|---|---|---|
| evolution | residue Cys50 is absolutely conserved, Cys50 is a component of the very long a-helix structure 2, which is composed of 25 amino acids. Residue Cys50 forms an active disulfide center with Cys45 | Homo sapiens |
| malfunction | as a common component in three 2-oxo acid dehydrogenase, a decrease in E3 activity affects the activities of all three complexes, which leads to increased urinary excretion of 2-oxo acids, elevated blood lactate, pyruvate, and branched chain amino acids. Patients with an E3 deficiency normally die young because an E3 deficiency is a critical genetic defect affecting the central nervous system. A deficiency in E3 results in Leigh syndrome with recurrent episodes of hypoglycemia and ataxia, permanent lactic acidaemia, and mental retardation. A C45A mutation results in a large decrease in human E3 activity and changes in the spectroscopic properties of human E3 | Homo sapiens |
| additional information | location of residue Cys50 in human E3 enzyme, structure comparisons with E3 enzymes from other species | Homo sapiens |
| physiological function | E3 is an essential component in pyruvate, 2-oxoglutarate and branched-chain 2-oxo acid dehydrogenase complexes. E3 catalyzes the reoxidation of a dihydrolipoyl prosthetic group attached to the lysyl residue(s) of the acyltransferase components of the three 2-oxo acid dehydrogenase complexes | Homo sapiens |
kcat/KM [mM/s]
| kcat/KM Value [1/mMs-1] | kcat/KM Value Maximum [1/mMs-1] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| 0.89 | - |
NAD+ | enzyme mutant C50A, pH 8.0, 37°C | Homo sapiens | |
| 2.3 | - |
NAD+ | enzyme mutant C50T, pH 8.0, 37°C | Homo sapiens | |
| 4731.6 | - |
NAD+ | wild-type enzyme, pH 8.0, 37°C | Homo sapiens | |
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