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Literature summary for 1.3.8.6 extracted from
- Potential complementation effects of two disease-associated mutations in tetrameric glutaryl-CoA dehydrogenase is due to inter subunit stability-activity counterbalance (2020), Biochim. Biophys. Acta, 1868, 140269 .
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| recombinant expression of C-terminally His6-tagged wild-type and mutant enzymes in Escherichia coli strain BL21(DE3) | Homo sapiens |
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| R227P | a naturally occuring GCDH disease-related mutation involved in glutaric aciduria type I (GA-I). Heterozygous patients harbouring the two mutations GCDH-p.Arg227Pro and GCDH-p.Val400Met show increased residual enzymatic activity in relation to homozygous patients with only one of the mutations, suggesting a complementation effect between the two. The mutant shows 95% reduced activity compared to wild-type | Homo sapiens |
| V400M | a naturally occuring GCDH disease-related mutation involved in glutaric aciduria type I (GA-I). Heterozygous patients harbouring the two mutations GCDH-p.Arg227Pro and GCDH-p.Val400Met show increased residual enzymatic activity in relation to homozygous patients with only one of the mutations, suggesting a complementation effect between the two. Thermal stress affects cofactor binding in the GCDH-p.Val400Met mutant. In vivo the p.Val400Met variant displays impaired interaction with the partner ETF, resulting in the lower values observed in patient fibroblasts. The mutant shows 24% reduced activity compared to wild-type | Homo sapiens |
KM Value [mM]
| KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| additional information | - |
additional information | Michaelis-Menten steady-state kinetic analysis for wild-type and mutant enzymes | Homo sapiens | |
| 0.02 | - |
glutaryl-CoA | recombinant mutant V400M with ETF, pH 7.8, temperature not specified in the publication | Homo sapiens |  |
| 0.0211 | - |
glutaryl-CoA | recombinant wild-type enzyme with ETF, pH 7.8, temperature not specified in the publication | Homo sapiens | |
| 0.0326 | - |
glutaryl-CoA | recombinant mutant R227P with ETF, pH 7.8, temperature not specified in the publication | 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. |
|---|---|---|---|---|---|---|
| glutaryl-CoA + electron-transfer flavoprotein | Homo sapiens | overall reaction | crotonyl-CoA + CO2 + reduced electron-transfer flavoprotein | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | Q92947 | - |
- |
Purification (Commentary)
| Purification (Comment) | Organism |
|---|---|
| recombinant His6-tagged wild-type and mutant enzymes from Escherichia coli strain BL21(DE3) by nickel affinity chromatography | Homo sapiens |
Specific Activity [micromol/min/mg]
| Specific Activity Minimum [µmol/min/mg] | Specific Activity Maximum [µmol/min/mg] | Comment | Organism |
|---|---|---|---|
| 5 | - |
recombinant mutant R227P with ETF, pH 7.8, temperature not specified in the publication | Homo sapiens |
| 70 | - |
recombinant mutant V400M with ETF, pH 7.8, temperature not specified in the publication | Homo sapiens |
| 112 | - |
recombinant mutant R227P with PMS, pH 7.8, temperature not specified in the publication | Homo sapiens |
| 205 | - |
recombinant wild-type enzyme with ETF, pH 7.8, temperature not specified in the publication | Homo sapiens |
| 1683 | - |
recombinant mutant V400M with PMS, pH 7.8, temperature not specified in the publication | Homo sapiens |
| 2224 | - |
recombinant wild-type enzyme with PMS, pH 7.8, temperature not specified in the publication | Homo sapiens |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| glutaryl-CoA + electron-transfer flavoprotein | overall reaction | Homo sapiens | crotonyl-CoA + CO2 + reduced electron-transfer flavoprotein | - |
? | |
| additional information | GCDH enzyme activity is measured following the reduction of DCPIP at 600 nm, with either PMS (artificial electron acceptor) or recombinant human ETF (GCDH natural electron acceptor), and glutaryl-CoA as electron donor, in 10 mM HEPES, pH 7.8 | Homo sapiens | ? | - |
- |
|
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| GCDH | - |
Homo sapiens |
| glutaryl-CoA dehydrogenase | - |
Homo sapiens |
Temperature Stability [°C]
| Temperature Stability Minimum [°C] | Temperature Stability Maximum [°C] | Comment | Organism |
|---|---|---|---|
| 43 | 53 | apparent thermal denaturation midpoint (Tm) of GCDH wild -type and mutants using different techniques, overview | Homo sapiens |
Turnover Number [1/s]
| Turnover Number Minimum [1/s] | Turnover Number Maximum [1/s] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| 0.6 | - |
glutaryl-CoA | recombinant mutant R227P with ETF, pH 7.8, temperature not specified in the publication | Homo sapiens | |
| 1.3 | - |
glutaryl-CoA | recombinant mutant V400M with ETF, pH 7.8, temperature not specified in the publication | Homo sapiens | |
| 3.1 | - |
glutaryl-CoA | recombinant wild-type enzyme with ETF, pH 7.8, temperature not specified in the publication | Homo sapiens | |
pH Optimum
| pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
|---|---|---|---|
| 7.8 | - |
assay at | Homo sapiens |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| electron transferring flavoprotein | ETF, the GCDH natural electron acceptor | Homo sapiens | |
| FAD | wild-type and mutant FAD binding structures, overview | Homo sapiens | |
| additional information | kinetics of flavin release, overview | Homo sapiens | |
| phenazine methosulfate | PMS, an artificial electron acceptor | Homo sapiens | |
General Information
| General Information | Comment | Organism |
|---|---|---|
| malfunction | glutaric aciduria type I (GA-I) is an autosomal recessive neurometabolic disease caused by mutations in the GCDH gene that encodes for glutaryl-CoA dehydrogenase (GCDH), a flavoprotein involved in the metabolism of tryptophan, lysine and hydroxylysin | Homo sapiens |
| metabolism | glutaryl-CoA dehydrogenase (GCDH), a flavoprotein, is involved in the metabolism of tryptophan, lysine and hydroxylysin | Homo sapiens |
| additional information | structure comparisons of wild-type and mutant enzyme proteins, FAD binding structures, overview | Homo sapiens |
kcat/KM [mM/s]
| kcat/KM Value [1/mMs-1] | kcat/KM Value Maximum [1/mMs-1] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| 18.4 | - |
glutaryl-CoA | recombinant mutant R227P with ETF, pH 7.8, temperature not specified in the publication | Homo sapiens | |
| 65 | - |
glutaryl-CoA | recombinant mutant V400M with ETF, pH 7.8, temperature not specified in the publication | Homo sapiens | |
| 146.92 | - |
glutaryl-CoA | recombinant wild-type enzyme with ETF, pH 7.8, temperature not specified in the publication | Homo sapiens | |
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