Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary extracted from

  • Birck, M.; Clinch, K.; Gainsford, G.; Schramm, V.; Tyler, P.
    Syntheses of 5-chlorouracils/thymines with 1-[phosphono(methyl/difluoromethyl)]-1,2-unsaturated-moiety-substituted methyl groups at N(1) and human thymidine phosphorylase inhibitory activity (2009), Helv. Chim. Acta, 92, 823-838.
No PubMed abstract available

Cloned(Commentary)

EC Number Cloned (Comment) Organism
2.4.2.4 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

EC Number Inhibitors Comment Organism Structure
2.4.2.4 1-[(R)-3-fluoro-2-(phosphonomethoxy)propyl]thymine
-
 Homo sapiens
2.4.2.4 3-benzoyl-5-chloropyrimidine-2,4(1H,3H)-dione
-
 Homo sapiens
2.4.2.4 5-ethyl-1-[(R)-3-fluoro-2-(phosphonomethoxy)propyl]uracil
-
 Homo sapiens
2.4.2.4 5-ethyl-1-[(R)-3-hydroxy-2-(phosphonomethoxy)propyl]uracil
-
 Homo sapiens
2.4.2.4 5-ethyl-1-[(S)-3-fluoro-2-(phosphonomethoxy)propyl]uracil
-
 Homo sapiens
2.4.2.4 5-methyluridine
-
 Homo sapiens
2.4.2.4 diethyl ((2-[(3,4-dihydro-5-methyl-2,4-dioxopyrimidin-1(2H)-yl)methyl]cyclopent-1-en-1-yl)(difluoro)methyl)phosphonate
-
 Homo sapiens
2.4.2.4 diethyl ((2-[(3,4-dihydro-5-methyl-2,4-dioxopyrimidin-1(2H)-yl)methyl]cyclopent-1-en-1-yl)methyl)phosphonate
-
 Homo sapiens
2.4.2.4 diethyl ((2-[(5-chloro-3,4-dihydro-2,4-dioxopyrimidin-1(2H)-yl)methyl]cyclopent-1-en-1-yl)methyl)phosphonate
-
 Homo sapiens
2.4.2.4 diethyl (2-[(5-chloro-3,4-dihydro-2,4-dioxopyrimidin-1(2H)-yl)methyl]benzyl)phosphonate
-
 Homo sapiens
2.4.2.4 diethyl ([2-(hydroxymethyl)cyclopent-1-en-1-yl]methyl)phosphonate
-
 Homo sapiens
2.4.2.4 diethyl [(Z)-4-(5-chloro-3,4-dihydro-2,4-dioxopyrimidin-1(2H)-yl)but-2-en-1-yl]phosphonate
-
 Homo sapiens
2.4.2.4 diethyl [(Z)-4-hydroxybut-2-en-1-yl]phosphonate
-
 Homo sapiens
2.4.2.4 diethyl [2-(hydroxymethyl)benzyl]phosphonate
-
 Homo sapiens
2.4.2.4 disodium ((2-[(3,4-dihydro-5-methyl-2,4-dioxopyrimidin-1(2H)-yl)methyl]cyclopent-1-en-1-yl)(difluoro)methyl)phosphonate
-
 Homo sapiens
2.4.2.4 disodium ((2-[(3,4-dihydro-5-methyl-2,4-dioxopyrimidin-1(2H)-yl)methyl]cyclopent-1-en-1-yl)methyl)phosphonate
-
 Homo sapiens
2.4.2.4 disodium ((2-[(5-chloro-3,4-dihydro-2,4-dioxopyrimidin-1(2H)-yl)methyl]cyclopent-1-en-1-yl)methyl)phosphonate
-
 Homo sapiens
2.4.2.4 disodium (2-[(5-chloro-3,4-dihydro-2,4-dioxopyrimidin-1(2H)-yl)methyl]benzyl)phosphonate
-
 Homo sapiens
2.4.2.4 disodium [(Z)-4-(5-chloro-3,4-dihydro-2,4-dioxopyrimidin-1(2H)-yl)but-2-en-1-yl]phosphonate
-
 Homo sapiens
2.4.2.4 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
2.4.2.4 uridine
-
 Homo sapiens

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
2.4.2.4 additional information
-
 additional information steady-state kinetics Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.4.2.4 thymidine + phosphate Homo sapiens
-
 thymine + 2-deoxy-alpha-D-ribose 1-phosphate
-
 r

Organism

EC Number Organism UniProt Comment Textmining
2.4.2.4 Homo sapiens
-
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
2.4.2.4 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 and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.4.2.4 2'-deoxy-5-nitrouridine + phosphate
-
 Homo sapiens 5-nitrouracil + 2-deoxy-alpha-D-ribose 1-phosphate
-
 ?
2.4.2.4 thymidine + phosphate
-
 Homo sapiens thymine + 2-deoxy-alpha-D-ribose 1-phosphate
-
 r

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
2.4.2.4 6
-
 assay at Homo sapiens

Ki Value [mM]

EC Number Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
2.4.2.4 0.013
-
 uridine pH 6.0, recombinant enzyme Homo sapiens
2.4.2.4 0.017
-
 5-methyluridine pH 6.0, recombinant enzyme Homo sapiens