Any feedback?
Literature summary for 2.1.1.45 extracted from
- Cooperative inhibition of human thymidylate synthase by mixtures of active site binding and allosteric inhibitors (2007), Biochemistry, 46, 2823-2830.
Application
| Application | Comment | Organism |
|---|---|---|
| medicine | inhibition of human thymidylate synthase leads to apoptosis of rapidly dividing cells such as cancer cells, human thymidylate synthase is a target in the chemotherapy of colorectal cancer and some other neoplasms | Homo sapiens |
Crystallization (Commentary)
| Crystallization (Comment) | Organism |
|---|---|
| hanging-drop vapour diffusion method | Homo sapiens |
| in complex with inhibitor 1,3-propanediphosphonic acid, to 2.5 A resolution | Homo sapiens |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| 1,3-propanediphosphonic acid | allosteric inhibitor of human thymidylate synthase; stabilizes an inactive conformer of loop 181-197. Mixed inhibitor of dUMP, uncompetitive inhibitor versus methylenetetrahydrofolate below 0.00025 mM, noncompetitive above 0.001 mM, respectively. 1,3-Propanediphosphonic acid shows positive cooperativity with antifolate inhibitor ZD9331. It leads to the formation of enzyme tetramers, but not of higher oligomers | Homo sapiens |  |
| ZD9331 | antifolate inhibitor, shows positive cooperativity with 1,3-propanediphosphonic acid | Homo sapiens | |
Molecular Weight [Da]
| Molecular Weight [Da] | Molecular Weight Maximum [Da] | Comment | Organism |
|---|---|---|---|
| 75000 | - |
dynamic light scattering | Homo sapiens |
| 148000 | - |
presence of inhibitor 1,3-propanediphosphonic acid, dynamic light scattering | Homo sapiens |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| 5,10-methylenetetrahydrofolate + dUMP | Homo sapiens | - |
7,8-dihydrofolate + dTMP | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | - |
- |
- |
| Homo sapiens | P04818 | - |
- |
Specific Activity [micromol/min/mg]
| Specific Activity Minimum [µmol/min/mg] | Specific Activity Maximum [µmol/min/mg] | Comment | Organism |
|---|---|---|---|
| 1.26 | - |
pH 7.2, 22°C | Homo sapiens |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| 5,10-methylenetetrahydrofolate + dUMP | - |
Homo sapiens | dihydrofolate + dTMP | - |
? | |
| 5,10-methylenetetrahydrofolate + dUMP | - |
Homo sapiens | 7,8-dihydrofolate + dTMP | - |
? | |
Subunits
| Subunits | Comment | Organism |
|---|---|---|
| dimer | X-ray diffraction | Homo sapiens |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| HTS | - |
Homo sapiens |
| human TS | - |
Homo sapiens |
Ki Value [mM]
| Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
|---|---|---|---|---|---|
| 0.000038 | - |
ZD9331 | pH 7.2, 22°C | Homo sapiens | |
| 0.0027 | - |
1,3-propanediphosphonic acid | pH 7.2, 22°C | Homo sapiens | |
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
