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Literature summary for 2.1.1.45 extracted from

  • Luo, B.; Repalli, J.; Yousef, A.M.; Johnson, S.R.; Lebioda, L.; Berger, S.H.
    Human thymidylate synthase with loop 181-197 stabilized in an inactive conformation: ligand interactions, phosphorylation, and inhibition profiles (2011), Protein Sci., 20, 87-94.
    View publication on PubMedView publication on EuropePMC
Search for more literature for 2.1.1.45

Cloned(Commentary)

Cloned (Comment) Organism
expressed in Escherichia coli strain TX61 Homo sapiens

Protein Variants

Protein Variants Comment Organism
A191K the mutant exhibits about 25% of the catalytic activity of the wild type enzyme. The mutant exhibits nonhyperbolic behavior with respect to dUMP and inhibition of catalysis is reversed by substrate saturation Homo sapiens
M190K the mutant exhibits less than1% of the catalytic activity of the wild type enzyme Homo sapiens
R163K the mutant exhibits an increase in catalytic activity and shows significantly reduced phosphorylation compared to the wild type enzyme Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
propylene diphosphonate mixed competitive-noncompetitive inhibitor with respect to dUMP Homo sapiens
ZD1694
-
 Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Posttranslational Modification

Posttranslational Modification Comment Organism
phosphoprotein phosphorylation of the wild type enzyme by casein kinase 2 is selective for the inactive conformation. dUMP inhibits phosphorylation of the wild type enzyme Homo sapiens

Substrates and Products (Substrate)

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

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.0000059
-
 propylene diphosphonate wild type enzyme, in 50 mM Tris-HCl, pH 7.4, 1 mM EDTA, 0.2% 2-mercaptoethanol, at 22°C Homo sapiens
0.0000113
-
 propylene diphosphonate mutant enzyme A191K, in 50 mM Tris-HCl, pH 7.4, 1 mM EDTA, 0.2% 2-mercaptoethanol, at 22°C Homo sapiens

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.00144
-
 wild type enzyme, in 50 mM Tris-HCl, pH 7.4, 1 mM EDTA, 0.2% 2-mercaptoethanol, at 22°C Homo sapiens ZD1694
0.034
-
 mutant enzyme A191K, in 50 mM Tris-HCl, pH 7.4, 1 mM EDTA, 0.2% 2-mercaptoethanol, at 22°C Homo sapiens ZD1694