Cloned (Comment) | Organism |
---|---|
expression of the calmodulin binding protein-tagged enzyme in Escherichia coli strain BL21(DE3) cells transformed with the pCal-n-EK/TP and pGroESL vectors | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
1-[(R)-3-fluoro-2-(phosphonomethoxy)propyl]thymine | - |
Homo sapiens | |
3-benzoyl-5-chloropyrimidine-2,4(1H,3H)-dione | - |
Homo sapiens | |
5-ethyl-1-[(R)-3-fluoro-2-(phosphonomethoxy)propyl]uracil | - |
Homo sapiens | |
5-ethyl-1-[(R)-3-hydroxy-2-(phosphonomethoxy)propyl]uracil | - |
Homo sapiens | |
5-ethyl-1-[(S)-3-fluoro-2-(phosphonomethoxy)propyl]uracil | - |
Homo sapiens | |
5-methyluridine | - |
Homo sapiens | |
diethyl ((2-[(3,4-dihydro-5-methyl-2,4-dioxopyrimidin-1(2H)-yl)methyl]cyclopent-1-en-1-yl)(difluoro)methyl)phosphonate | - |
Homo sapiens | |
diethyl ((2-[(3,4-dihydro-5-methyl-2,4-dioxopyrimidin-1(2H)-yl)methyl]cyclopent-1-en-1-yl)methyl)phosphonate | - |
Homo sapiens | |
diethyl ((2-[(5-chloro-3,4-dihydro-2,4-dioxopyrimidin-1(2H)-yl)methyl]cyclopent-1-en-1-yl)methyl)phosphonate | - |
Homo sapiens | |
diethyl (2-[(5-chloro-3,4-dihydro-2,4-dioxopyrimidin-1(2H)-yl)methyl]benzyl)phosphonate | - |
Homo sapiens | |
diethyl ([2-(hydroxymethyl)cyclopent-1-en-1-yl]methyl)phosphonate | - |
Homo sapiens | |
diethyl [(Z)-4-(5-chloro-3,4-dihydro-2,4-dioxopyrimidin-1(2H)-yl)but-2-en-1-yl]phosphonate | - |
Homo sapiens | |
diethyl [(Z)-4-hydroxybut-2-en-1-yl]phosphonate | - |
Homo sapiens | |
diethyl [2-(hydroxymethyl)benzyl]phosphonate | - |
Homo sapiens | |
disodium ((2-[(3,4-dihydro-5-methyl-2,4-dioxopyrimidin-1(2H)-yl)methyl]cyclopent-1-en-1-yl)(difluoro)methyl)phosphonate | - |
Homo sapiens | |
disodium ((2-[(3,4-dihydro-5-methyl-2,4-dioxopyrimidin-1(2H)-yl)methyl]cyclopent-1-en-1-yl)methyl)phosphonate | - |
Homo sapiens | |
disodium ((2-[(5-chloro-3,4-dihydro-2,4-dioxopyrimidin-1(2H)-yl)methyl]cyclopent-1-en-1-yl)methyl)phosphonate | - |
Homo sapiens | |
disodium (2-[(5-chloro-3,4-dihydro-2,4-dioxopyrimidin-1(2H)-yl)methyl]benzyl)phosphonate | - |
Homo sapiens | |
disodium [(Z)-4-(5-chloro-3,4-dihydro-2,4-dioxopyrimidin-1(2H)-yl)but-2-en-1-yl]phosphonate | - |
Homo sapiens | |
additional information | synthesis of 5-alkyl, 5-aryl, or 5-fluoro derivatives of 1-[2-(phosphonomethoxy)-ethyl]thymine inhibitors that mimic the interatomic distance between the incoming phosphate and leaving pyrimidine groups at the transition state for the putative SN2 mechanism of thymidine phosphorylase, structures, the inhibitors are not effective compared to (phosphonomethoxy)-alkyl-pyrimidine inhibitors, overview. Switching the N1-linked side chains found in 1-[2-(phosphonomethoxy)-ethyl]thymine, 1-[(R)-3-hydroxy-2-(phosphonomethoxy)propyl]thymine and 1-[(R)-3-fluoro-2-(phosphonomethoxy)propyl]thymine to the N3-position of the nucleobases resulted in significant loss of activity. Replacement of the iminopyrrolidine ring found in 5-ethyl-1-[(R)-3-hydroxy-2-(phosphonomethoxy)propyl]uracil with a 3-methylimidazol-3-ium ring leads to a series of less active 5-halo-6-[(3-methylimidazol-3-ium-1-yl)methyl]-uracil chlorides. On the other hand, replacement with a 2-aminoimidazole ring, leads to a number of 6-[(2-aminoimidazol-1-yl)methyl]-5-chloro-(and 5-bromo)uracil hydrochlorides with similar inhibitory strength compared to 5-ethyl-1-[(R)-3-hydroxy-2-(phosphonomethoxy)propyl]uracil, computer-modeling simulations, overview | Homo sapiens | |
uridine | - |
Homo sapiens |
KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
additional information | - |
additional information | steady-state kinetics | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
thymidine + phosphate | Homo sapiens | - |
thymine + 2-deoxy-alpha-D-ribose 1-phosphate | - |
r |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
- |
- |
Purification (Comment) | Organism |
---|---|
recombinant enzyme from Escherichia coli strain BL21(DE3) by calmodulin affinity chromatography, cleavage of the calmodulin binding protein tag by enterokinase, removal by chromatography on soybean trypsin inhibitor-sepharose | Homo sapiens |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
2'-deoxy-5-nitrouridine + phosphate | - |
Homo sapiens | 5-nitrouracil + 2-deoxy-alpha-D-ribose 1-phosphate | - |
? | |
thymidine + phosphate | - |
Homo sapiens | thymine + 2-deoxy-alpha-D-ribose 1-phosphate | - |
r |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
6 | - |
assay at | Homo sapiens |
Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
---|---|---|---|---|---|
0.013 | - |
uridine | pH 6.0, recombinant enzyme | Homo sapiens | |
0.017 | - |
5-methyluridine | pH 6.0, recombinant enzyme | Homo sapiens |