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 (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 | 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 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 | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
5,10-methylenetetrahydrofolate + dUMP | Homo sapiens | - |
7,8-dihydrofolate + dTMP | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
- |
- |
Homo sapiens | P04818 | - |
- |
Specific Activity Minimum [µmol/min/mg] | Specific Activity Maximum [µmol/min/mg] | Comment | Organism |
---|---|---|---|
1.26 | - |
pH 7.2, 22°C | Homo sapiens |
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 | Comment | Organism |
---|---|---|
dimer | X-ray diffraction | Homo sapiens |
Synonyms | Comment | Organism |
---|---|---|
HTS | - |
Homo sapiens |
human TS | - |
Homo sapiens |
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 |