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Literature summary extracted from

  • Lovelace, L.L.; Gibson, L.M.; Lebioda, L.
    Cooperative inhibition of human thymidylate synthase by mixtures of active site binding and allosteric inhibitors (2007), Biochemistry, 46, 2823-2830.
    View publication on PubMedView publication on EuropePMC

Application

EC Number Application Comment Organism
2.1.1.45 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)

EC Number Crystallization (Comment) Organism
2.1.1.45 hanging-drop vapour diffusion method Homo sapiens
2.1.1.45 in complex with inhibitor 1,3-propanediphosphonic acid, to 2.5 A resolution Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
2.1.1.45 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
2.1.1.45 ZD9331 antifolate inhibitor, shows positive cooperativity with 1,3-propanediphosphonic acid Homo sapiens

Molecular Weight [Da]

EC Number Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
2.1.1.45 75000
-
 dynamic light scattering Homo sapiens
2.1.1.45 148000
-
 presence of inhibitor 1,3-propanediphosphonic acid, dynamic light scattering Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.1.1.45 5,10-methylenetetrahydrofolate + dUMP Homo sapiens
-
 7,8-dihydrofolate + dTMP
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
2.1.1.45 Homo sapiens
-
-
-
2.1.1.45 Homo sapiens P04818
-
-

Specific Activity [micromol/min/mg]

EC Number Specific Activity Minimum [µmol/min/mg] Specific Activity Maximum [µmol/min/mg] Comment Organism
2.1.1.45 1.26
-
 pH 7.2, 22°C Homo sapiens

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.1.1.45 5,10-methylenetetrahydrofolate + dUMP
-
 Homo sapiens dihydrofolate + dTMP
-
 ?
2.1.1.45 5,10-methylenetetrahydrofolate + dUMP
-
 Homo sapiens 7,8-dihydrofolate + dTMP
-
 ?

Subunits

EC Number Subunits Comment Organism
2.1.1.45 dimer X-ray diffraction Homo sapiens

Synonyms

EC Number Synonyms Comment Organism
2.1.1.45 HTS
-
 Homo sapiens
2.1.1.45 human TS
-
 Homo sapiens

Ki Value [mM]

EC Number Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
2.1.1.45 0.000038
-
 ZD9331 pH 7.2, 22°C Homo sapiens
2.1.1.45 0.0027
-
 1,3-propanediphosphonic acid pH 7.2, 22°C Homo sapiens