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Literature summary for 5.1.1.18 extracted from
- Human serine racemase is nitrosylated at multiple sites (2018), Biochim. Biophys. Acta, 1866, 813-821 .
Activating Compound
| Activating Compound | Comment | Organism | Structure |
|---|---|---|---|
| ATP | activates | Homo sapiens |  |
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| sequence comparisons, recombinant expression of His6-tagged wild-type and mutant enzymes in Escherichia coli strain BL21 CodonPlus (DE3)-RIL | Homo sapiens |
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| C113S | site-directed mutagenesis, the C113S mutant exhibits a KM for L-serine which is 3.5fold higher than for the wild-type enzyme and a 3.3fold lower specific activity. ATP binding to the mutant in the presence of L-serine occurs with a 5fold higher EC50 compared to wild-type, with conserved binding cooperativity. Phenotype, overview | Homo sapiens |
| D318N | site-directed mutagenesis | Homo sapiens |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| S-nitrosoglutathione | GSNO, inhibition of human serine racemase by S-nitrosylation at Cys133, Cys128,and Cys269. The time-course is markedly biphasic, with a fast phase associated with the reaction of Cys113. The inhibition results from a conformational change rather than the direct displacement of ATP. Effect of nitrosylation on the cross-talk between ATP binding site and active site, both ATP and glycine bind to their respective sites with the same affinity regardless of the nitrosylation state | Homo sapiens | |
KM Value [mM]
| KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| additional information | - |
additional information | kinetics of wild-type and mutant enzymes | Homo sapiens | |
| 16 | - |
L-serine | pH 8.0, 37°C, recombinant wild-type enzyme | Homo sapiens | |
| 50 | - |
L-serine | pH 8.0, 37°C, recombinant mutant D318N | Homo sapiens | |
| 54 | - |
L-serine | pH 8.0, 37°C, recombinant mutant C113S | Homo sapiens | |
Metals/Ions
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| Mg2+ | required | Homo sapiens | |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| L-serine | Homo sapiens | - |
D-serine | - |
r | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | Q9GZT4 | - |
- |
Posttranslational Modification
| Posttranslational Modification | Comment | Organism |
|---|---|---|
| S-nitrosylation | human serine racemase is nitrosylated at multiple sites, which inhibits the enzyme activity. Besides Cys113, two additional cysteine residues, Cys269, unique to the human orthologue, and Cys128, are recognized as S-nitrosylation sites through mass spectrometry and site-directed mutagenesis. S-nitrosylation produces a partial interruption of the cross-talk between the ATP binding site and the active site. The inhibition results from a conformational change rather than the direct displacement of ATP | Homo sapiens |
Purification (Commentary)
| Purification (Comment) | Organism |
|---|---|
| recombinant His6-tagged wild-type and mutant enzymes from Escherichia coli strain BL21 CodonPlus (DE3)-RIL | Homo sapiens |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| L-serine | - |
Homo sapiens | D-serine | - |
r | |
Subunits
| Subunits | Comment | Organism |
|---|---|---|
| monomer | crystal structure analysis, PDB ID 3L6B | Homo sapiens |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| hSR | - |
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 |
|---|---|---|---|---|---|
| 0.85 | - |
L-serine | pH 8.0, 37°C, recombinant mutant C113S | Homo sapiens | |
| 1.92 | - |
L-serine | pH 8.0, 37°C, recombinant mutant D318N | Homo sapiens | |
| 2.77 | - |
L-serine | pH 8.0, 37°C, recombinant wild-type enzyme | Homo sapiens | |
pH Optimum
| pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
|---|---|---|---|
| 8 | - |
assay at | Homo sapiens |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| pyridoxal 5'-phosphate | - |
Homo sapiens | |
Ki Value [mM]
| Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
|---|---|---|---|---|---|
| additional information | - |
additional information | biphasic inhibition kinetics via S-nitrosylation | Homo sapiens |
General Information
| General Information | Comment | Organism |
|---|---|---|
| physiological function | serine racemase is a pyridoxal 5'-phosphate dependent enzyme responsible for the synthesis of D-serine, a neuromodulator of the NMDA receptors. Its activity is modulated by several ligands, including ATP, divalent cations and protein interactors. The enzyme is negatively regulated by reversible S-nitrosylation of cysteine residues, C113, C128, and C269, overview | Homo sapiens |
kcat/KM [mM/s]
| kcat/KM Value [1/mMs-1] | kcat/KM Value Maximum [1/mMs-1] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| 0.016 | - |
L-serine | pH 8.0, 37°C, recombinant mutant C113S | Homo sapiens | |
| 0.038 | - |
L-serine | pH 8.0, 37°C, recombinant mutant D318N | Homo sapiens | |
| 0.17 | - |
L-serine | pH 8.0, 37°C, recombinant wild-type enzyme | Homo sapiens | |
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Release 2023.1 (January 2023)
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