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Literature summary for 1.14.16.4 extracted from
- Characterization of wild-type and mutant forms of human tryptophan hydroxylase 2 (2007), J. Neurochem., 100, 1648-1657.
Activating Compound
| Activating Compound | Comment | Organism | Structure |
|---|---|---|---|
| DTT | - |
Homo sapiens |  |
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| expression as maltose-binding protein fusion protein in Escherichia coli | Homo sapiens |
| gene tph2, expression of TPH2 wild-type and mutants in Escherichia coli and in HEK-293 cells | Homo sapiens |
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| additional information | effects of TPH2 mutations on their heterologous expression levels, solubility, thermal stability, secondary structure, and catalytic properties, overview | Homo sapiens |
| P449R | reduced thermal stability compared to the wild-type enzyme | Homo sapiens |
| P449R | site-directed mutagenesis, the TPH2 genetic variant, shows comparable catalytic activity (Vmax) and solubility relative to the wild type, but has decreased thermal stability | Homo sapiens |
| R441H | reduced solubility compared to the wild-type enzyme and reduced thermal stability. The mutant shows a 2fold lower Km for (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin | Homo sapiens |
| R441H | site-directed mutagenesis, the TPH2 genetic variant, shows had decreased activity, solubility and stability compared to the wild-type enzyme | Homo sapiens |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| dopamine | 50% inhibition at 32 microM | Homo sapiens | |
KM Value [mM]
| KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| additional information | - |
additional information | isozymes TPH1 and TPH2 kinetics, overview | Homo sapiens | |
| 0.0147 | - |
tetrahydrobiopterin | pH 7.0, 30°C, recombinant mutant P449R fusion enzyme | Homo sapiens | |
| 0.0186 | - |
L-tryptophan | pH 7.0, 30°C, recombinant mutant R441H fusion enzyme | Homo sapiens | |
| 0.0217 | - |
tetrahydrobiopterin | pH 7.0, 30°C, recombinant wild-type TPH2 fusion enzyme | Homo sapiens | |
| 0.0249 | - |
tetrahydrobiopterin | pH 7.0, 30°C, recombinant mutant R441H fusion enzyme | Homo sapiens | |
| 0.0255 | - |
L-tryptophan | pH 7.0, 30°C, recombinant mutant P449R fusion enzyme | Homo sapiens | |
| 0.0282 | - |
L-tryptophan | pH 7.0, 30°C, recombinant wild-type TPH2 fusion enzyme | Homo sapiens | |
| 0.0289 | - |
tetrahydrobiopterin | pH 7.0, 30°C, recombinant detagged mutant R441H | Homo sapiens | |
| 0.0334 | - |
L-tryptophan | pH 7.0, 30°C, recombinant detagged mutant R441H | Homo sapiens | |
| 0.0413 | - |
L-tryptophan | - |
Homo sapiens | |
| 0.0413 | - |
L-tryptophan | pH 7.0, 30°C, recombinant detagged wild-type TPH2 | Homo sapiens | |
| 0.0511 | - |
L-tryptophan | pH 7.0, 30°C, recombinant detagged mutant P449R | Homo sapiens | |
| 0.0518 | - |
tetrahydrobiopterin | pH 7.0, 30°C, recombinant detagged mutant P449R | Homo sapiens | |
| 0.0684 | - |
(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin | - |
Homo sapiens | |
| 0.0684 | - |
tetrahydrobiopterin | pH 7.0, 30°C, recombinant detagged wild-type TPH2 | Homo sapiens | |
Molecular Weight [Da]
| Molecular Weight [Da] | Molecular Weight Maximum [Da] | Comment | Organism |
|---|---|---|---|
| 240300 | - |
gel-filtration | Homo sapiens |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| L-tryptophan + tetrahydrobiopterin + O2 | Homo sapiens | rate-limiting step in the biosynthesis of serotonin, regulation of isozymes TPH1 and TPH2, overview | 5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | - |
- |
- |
| Homo sapiens | Q8IWU9 | genes tph1 and tph2 | - |
Purification (Commentary)
| Purification (Comment) | Organism |
|---|---|
| recombinant His6-MBP-fusion TPH2 wild-type and mutants from Escherichia coli by affinity chromatography, fusion protein cleavage, and gel filtration | Homo sapiens |
| two chromatography steps | Homo sapiens |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| cell culture | - |
Homo sapiens | - |
Specific Activity [micromol/min/mg]
| Specific Activity Minimum [µmol/min/mg] | Specific Activity Maximum [µmol/min/mg] | Comment | Organism |
|---|---|---|---|
| 0.000064 | - |
recombinant mutant R441H TPH2 in HEK-293 cells | Homo sapiens |
| 0.00052 | - |
recombinant wild-type TPH2 in HEK-293 cells | Homo sapiens |
| 0.00165 | - |
recombinant mutant P449R TPH2 in HEK-293 cells | Homo sapiens |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| L-tryptophan + (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + O2 | - |
Homo sapiens | 5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin | - |
? | |
| L-tryptophan + tetrahydrobiopterin + O2 | - |
Homo sapiens | 5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin | - |
? | |
| L-tryptophan + tetrahydrobiopterin + O2 | rate-limiting step in the biosynthesis of serotonin, regulation of isozymes TPH1 and TPH2, overview | Homo sapiens | 5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin | - |
? | |
Subunits
| Subunits | Comment | Organism |
|---|---|---|
| tetramer | structure molecular modelling of TPH2 wild-type and mutants | Homo sapiens |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| TPH2 | - |
Homo sapiens |
| tryptophan hydroxylase | - |
Homo sapiens |
| tryptophan hydroxylase 2 | - |
Homo sapiens |
Temperature Optimum [°C]
| Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
|---|---|---|---|
| 30 | - |
assay at | Homo sapiens |
pH Optimum
| pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
|---|---|---|---|
| 7 | - |
assay at | Homo sapiens |
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