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

BRENDA support

Literature summary extracted from

  • Luo, Y.; Walla, M.; Wyatt, M.D.
    Uracil incorporation into genomic DNA does not predict toxicity caused by chemotherapeutic inhibition of thymidylate synthase (2008), DNA Repair, 7, 162-169.
    View publication on PubMedView publication on EuropePMC

Application

EC Number Application Comment Organism
2.1.1.45 medicine thymidylate synthase is an important target of several chemotherapeutic agents including 5-fluorouracil and raltitrexed Homo sapiens

Protein Variants

EC Number Protein Variants Comment Organism
2.1.1.45 additional information construction of a cell line expressing the Ugi protein inhibitor of UNG family of uracil DNA glycosylases, which reduces cellular uracil DNA glycosylase activity by at least 45-fold. Genomic uracil levels are increased over 4fold following thymidylate synthase inhibition in the Ugi-expressing cells, but do not detectably increase in UNG proficient cells. No difference in toxicity between the UNG proficient and UNG-inhibited cells to folate or nucleotide-based inhibitors of thymidylate synthase. UNG proficient and UNG-inhibited cells arrest in early S-phase and resume replication progression during recovery from raltitrexed treatment almost identically Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
2.1.1.45 5-fluorouracil 5-FU Homo sapiens
2.1.1.45 capecitabine prodrug of 5-fluorouracil Homo sapiens
2.1.1.45 raltitrexed
-
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 N5,N10-methylenetetrahydrofolate + dUMP Homo sapiens during thymidylate synthase inhibition, TMP levels decrease with a subsequent increase in dUTP 7,8-dihydrofolate + TMP
-
?

Organism

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

Source Tissue

EC Number Source Tissue Comment Organism Textmining
2.1.1.45 HEK-293 cell additionally transfected with pLGC-hUgi and pLGCX plasmids Homo sapiens
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.1.1.45 N5,N10-methylenetetrahydrofolate + dUMP
-
Homo sapiens 7,8-dihydrofolate + TMP
-
?
2.1.1.45 N5,N10-methylenetetrahydrofolate + dUMP during thymidylate synthase inhibition, TMP levels decrease with a subsequent increase in dUTP Homo sapiens 7,8-dihydrofolate + TMP
-
?