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Information on EC 2.1.1.45 - thymidylate synthase
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2.1.1.45 thymidylate synthaseSpecify your search results
Word Map
- 2.1.1.45
- 5-fluorouracil
- thymidine
- colorectal
- dihydrofolate
- antifolate
- dihydropyrimidine
- methotrexate
- pyrimidine
- phosphorylase
-
fluoropyrimidine
-
resect
- ribonucleotide
- pemetrexed
-
adjuvant
- fdump
- leucovorin
- mthfr
- polyglutamates
- uracil
-
non-small
-
casey
-
schedule
-
5-fu-based
- cisplatin
- oxaliplatin
- 5-fluoro-2'-deoxyuridine
-
antimetabolite
- orotate
- irinotecan
- deoxyuridine
- capecitabine
- folylpolyglutamate
-
folinic
-
polyglutamylation
- glycinamide
- dttp
-
folate-dependent
- medicine
-
formyltransferase
-
ccrf-cem
-
tegafur
- 2'-deoxyuridine
- gemcitabine
- quinazoline
- deoxythymidine
- aminopterin
-
cross-complementing
-
5-fu-induced
-
transformylase
- drug development
- deoxycytidylate
-
methotrexate-resistant
The enzyme appears in viruses and cellular organisms
Synonyms
BgDHFR-TS, bifunctional TS-DHFR, DFR-TS, DHFR-TS, DHFR–TS, dihydrofolate reductase-thymidylate synthase, dTMP synthase, HTS, human TS, LBRM_06_0830, 
more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
DHFR-TS
dihydrofolate reductase-thymidylate synthase
dTMP synthase
-
-
-
-
methylenetetrahydrofolate:dUMP C-methyltransferase
-
-
-
-
ThyA
thymidylate synthase A
thymidylate synthase-dihydrofolate reductase
thymidylate synthetase
TMP synthetase
-
-
-
-
TS-DHFR
TSase
TYMS
Y110A7A.4
additional information
thymidylate synthetase
-
-
-
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
5,10-methylenetetrahydrofolate + dUMP = dihydrofolate + dTMP
-
-
-
-
5,10-methylenetetrahydrofolate + dUMP = dihydrofolate + dTMP
O2 and methylenetetrahydrofolate compete for the reduced enzyme after dUMP binding. dUMP enhances the rate of the oxidative half reaction and while the oxidase reaction is faster than the reaction with methylenetetrahydrofolate, this cofactor slows down the consumption of NADPH in the presence of O2 in accordance with substrate competition. dUMP, the substrate of the oxidative half reaction does not affect the reductive half reaction. In the absence of the second substrate methylenetetrahydrofolate, dUMP enhances the reaction of molecular oxygen with the reduced enzyme
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dehalogenation
-
-
-
-
methylene group transfer
-
-
-
-
reductive methylation
reductive methylation
-
-
-
-
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PATHWAY SOURCE
PATHWAYS
BRENDA
MetaCyc
folate transformations II (plants), folate transformations III (E. coli), pyrimidine deoxyribonucleosides salvage, pyrimidine deoxyribonucleotides biosynthesis from CTP, pyrimidine deoxyribonucleotides de novo biosynthesis I, pyrimidine deoxyribonucleotides de novo biosynthesis II, pyrimidine deoxyribonucleotides de novo biosynthesis IV, superpathway of pyrimidine deoxyribonucleotides de novo biosynthesis (E. coli)
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SYSTEMATIC NAME
IUBMB Comments
5,10-methylenetetrahydrofolate:dUMP C-methyltransferase
-
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CAS REGISTRY NUMBER
COMMENTARY
9031-61-2
-
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(-)-tetrahydropteroylglutamate + 2'-deoxyuridine 5'-monophosphate
7,8-dihydropteroylglutamate + thymidine phosphate
(6R)-N5,N10-methylene-5,6,7,8-tetrahydrofolate + 2'-deoxyuridylate
7,8-dihydrofolate + 5-methyl-2'-deoxyuridylate
(6S)-methylenetetrahydropteroylhexaglutamate + 2'-deoxyuridylate
7,8-dihydropteroylhexaglutamate + thymidine phosphate
-
-
-
-
r
(6S)-tetrahydropteroylglutamate + 2-deoxyuridylate
7,8-dihydropteroylglutamate + thymidine phosphate
(6S)-tetrahydropteroyltriglutamate + 2'-deoxyuridylate
7,8-dihydropteroyltriglutamate + thymidine phosphate
-
-
-
-
r
(R)-5,10-methylene-5,6,7,8-tetrahydrofolate + dUMP
7,8-dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + 2'-deoxycytidine 5'-monophosphate
dihydrofolate + cytidine phosphate
5,10-methylenetetrahydrofolate + 2'-fluoro-2'-deoxyuridine 5'-phosphate
7,8-dihydrofolate + ?
5,10-methylenetetrahydrofolate + 5'-fluoro-2'-deoxyuridine 5'-phosphate
7,8-dihydrofolate + ?
-
some mutants are capable of forming covalent thymidylate synthase-5-fluoro-dUMP-methylenetetrahydrofolate complex
-
-
?
5,10-methylenetetrahydrofolate + deoxyuridine monophosphate
7,8-dihydrofolate + deoxythymidine monophosphate
-
-
-
?
5,10-methylenetetrahydrofolylheptaglutamate + 2'-deoxyuridylate
7,8-dihydrofolylheptaglutamate + thymidine phosphate
-
-
-
-
r
5,10-methylenetetrahydrofolylpentaglutamate + 2'-deoxyuridylate
7,8-dihydrofolylpentaglutamate + thymidine phosphate
-
-
-
-
r
5,10-methylenetetrahydropteroylheptaglutamate + 2'-deoxyuridylate
7,8-dihydropteroylheptaglutamate + thymidine phosphate
5,10-methylenetetrahydropteroylpentaglutamate + 2'-deoxyuridylate
7,8-dihydropteroylpentaglutamate + thymidine phosphate
N5,10-methylenetetrahydrofolate + 2'-deoxyuridine 5'-dithiophosphate
7,8-dihydrofolate + ?
N5,10-methylenetetrahydrofolate + 5-hydroxy-2'-deoxyuridine 5'-monophosphate
7,8-dihydrofolate + ?
-
-
-
-
?
(-)-tetrahydropteroylglutamate + 2'-deoxyuridine 5'-monophosphate
7,8-dihydropteroylglutamate + thymidine phosphate
-
-
-
-
-
(-)-tetrahydropteroylglutamate + 2'-deoxyuridine 5'-monophosphate
7,8-dihydropteroylglutamate + thymidine phosphate
-
-
-
-
?
(-)-tetrahydropteroylglutamate + 2'-deoxyuridine 5'-monophosphate
7,8-dihydropteroylglutamate + thymidine phosphate
Escherichia coli B / ATCC 11303
-
-
-
-
-
(-)-tetrahydropteroylglutamate + 2'-deoxyuridine 5'-monophosphate
7,8-dihydropteroylglutamate + thymidine phosphate
Escherichia coli B / ATCC 11303
-
-
-
-
?
(6R)-N5,N10-methylene-5,6,7,8-tetrahydrofolate + 2'-deoxyuridylate
7,8-dihydrofolate + 5-methyl-2'-deoxyuridylate
-
-
-
r
(6R)-N5,N10-methylene-5,6,7,8-tetrahydrofolate + 2'-deoxyuridylate
7,8-dihydrofolate + 5-methyl-2'-deoxyuridylate
-
-
-
-
r
(6S)-tetrahydropteroylglutamate + 2-deoxyuridylate
7,8-dihydropteroylglutamate + thymidine phosphate
-
-
-
-
-
(6S)-tetrahydropteroylglutamate + 2-deoxyuridylate
7,8-dihydropteroylglutamate + thymidine phosphate
-
-
-
-
r
(6S)-tetrahydropteroylglutamate + 2-deoxyuridylate
7,8-dihydropteroylglutamate + thymidine phosphate
-
-
-
-
-
(6S)-tetrahydropteroylglutamate + 2-deoxyuridylate
7,8-dihydropteroylglutamate + thymidine phosphate
-
-
-
-
-
(6S)-tetrahydropteroylglutamate + 2-deoxyuridylate
7,8-dihydropteroylglutamate + thymidine phosphate
-
-
-
-
-
5,10-methylene-5,6,7,8-tetrahydrofolate + dUMP
7,8-dihydrofolate + dTMP
-
-
-
-
?
5,10-methylene-5,6,7,8-tetrahydrofolate + dUMP
7,8-dihydrofolate + dTMP
-
-
-
-
-
5,10-methylene-5,6,7,8-tetrahydrofolate + dUMP
7,8-dihydrofolate + dTMP
-
-
-
-
?
5,10-methylene-5,6,7,8-tetrahydrofolate + dUMP
7,8-dihydrofolate + dTMP
-
thymidylate synthase is the third enzyme in the methylene tetrahydrofolate cycle besides dihydrofolate reductase and serine hydroxymethyltransferase, in many organisms, thymidylate synthase is the only de novo source for dTMP required for DNA synthesis
-
-
?
5,10-methylene-5,6,7,8-tetrahydrofolate + dUMP
7,8-dihydrofolate + dTMP
-
-
-
-
-
5,10-methylene-5,6,7,8-tetrahydrofolate + dUMP
7,8-dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + 2'-deoxycytidine 5'-monophosphate
dihydrofolate + cytidine phosphate
-
only mutant TS N229D
-
-
?
5,10-methylenetetrahydrofolate + 2'-deoxycytidine 5'-monophosphate
dihydrofolate + cytidine phosphate
-
only mutant TS N229D
-
-
?
5,10-methylenetetrahydrofolate + 2'-fluoro-2'-deoxyuridine 5'-phosphate
7,8-dihydrofolate + ?
-
-
-
-
?
5,10-methylenetetrahydrofolate + 2'-fluoro-2'-deoxyuridine 5'-phosphate
7,8-dihydrofolate + ?
Escherichia coli B / ATCC 11303
-
-
-
-
?
5,10-methylenetetrahydrofolate + 2'-fluoro-2'-deoxyuridine 5'-phosphate
7,8-dihydrofolate + ?
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
7,8-dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
7,8-dihydrofolate + dTMP
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
7,8-dihydrofolate + dTMP
thymidylate synthase is essential for de novo synthesis of dTMP and is a key enzyme involved in DNA synthesis and transcriptional regulation of organisms
-
-
?
5,10-methylenetetrahydrofolate + dUMP
7,8-dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
7,8-dihydrofolate + dTMP
-
inhibition of thymidylate synthase or of DHFR leads to thymineless death of eukaryotic organisms
-
-
?
5,10-methylenetetrahydrofolate + dUMP
7,8-dihydrofolate + dTMP
-
it is a key enzyme for the synthesis of the DNA-specific nucleotide thymidylate
-
-
?
5,10-methylenetetrahydrofolate + dUMP
7,8-dihydrofolate + dTMP
-
thymidylate synthase catalyses the only de novo pathway to produce thymidylate for DNA replication and repair
-
-
?
5,10-methylenetetrahydrofolate + dUMP
7,8-dihydrofolate + dTMP
-
thymidylate synthase is a key enzyme in the de novo synthesis of dTMP
-
-
?
5,10-methylenetetrahydrofolate + dUMP
7,8-dihydrofolate + dTMP
-
TS is a key enzyme in folate metabolism
-
-
?
5,10-methylenetetrahydrofolate + dUMP
7,8-dihydrofolate + dTMP
-
mTHF, TS is the sole source of de novo thymidylate which is required for DNA synthesis
-
-
?
5,10-methylenetetrahydrofolate + dUMP
7,8-dihydrofolate + dTMP
-
thymidylate synthase is an essential enzyme for de novo synthesis of thymidylate (dTMP), a precursor for DNA synthesis
-
-
?
5,10-methylenetetrahydrofolate + dUMP
7,8-dihydrofolate + dTMP
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
7,8-dihydrofolate + TMP
-
during TS inhibition, TMP levels decrease with a subsequent increase in dUTP
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
r
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
key function in DNA synthesis, repair and cell division
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
biosynthesis of thymidylic acid, only de novo source of thymidine, crucial for DNA replication in every organism
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
r
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
r
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
r
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
r
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?, r
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
r
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
r
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
biosynthesis of thymidylic acid, only de novo source of thymidine, crucial for DNA replication in every organism
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
?, r
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
r
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
biosynthesis of thymidylic acid, only de novo source of thymidine, crucial for DNA replication in every organism
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?, r
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
r
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
r
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
r
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
reverse reaction is at least 630times slower than the forward reaction
-
-
r
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
key function in DNA synthesis, repair and cell division
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
biosynthesis of thymidylic acid, only de novo source of thymidine, crucial for DNA replication in every organism
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
r
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
485357, 485363, 485365, 485369, 485371, 485372, 485374, 485382, 485383, 485388, 485397, 485402, 485406, 485409, 485413, 485416, 485417
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
485357, 485359, 485363, 485365, 485369, 485371, 485372, 485373, 485374, 485375, 485376, 485380, 485381, 485382, 485383, 485388, 485389, 485397, 485402, 485405, 485406, 485408, 485409, 485413, 485415, 485416, 485417
-
-
r
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
r
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
reverse reaction is at least 630times slower than the forward reaction
-
-
r
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
key function in DNA synthesis, repair and cell division
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
biosynthesis of thymidylic acid, only de novo source of thymidine, crucial for DNA replication in every organism
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
Escherichia coli B / ATCC 11303
-
-
-
-
?, r
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
Escherichia coli B / ATCC 11303
-
-
-
-
?, r
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
Escherichia coli B / ATCC 11303
-
-
-
-
?, r
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
Escherichia coli B / ATCC 11303
-
-
-
-
?, r
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
Escherichia coli B / ATCC 11303
-
-
-
-
r
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
Escherichia coli B / ATCC 11303
-
key function in DNA synthesis, repair and cell division
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
Escherichia coli B / ATCC 11303
-
-
-
-
r
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
Escherichia coli B / ATCC 11303
-
key function in DNA synthesis, repair and cell division
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
Escherichia coli B / ATCC 11303
-
biosynthesis of thymidylic acid, only de novo source of thymidine, crucial for DNA replication in every organism
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
Escherichia coli B / ATCC 11303
-
-
-
-
r
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
Escherichia coli B / ATCC 11303
-
biosynthesis of thymidylic acid, only de novo source of thymidine, crucial for DNA replication in every organism
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
Escherichia coli B / ATCC 11303
-
-
-
-
r
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
Escherichia coli B / ATCC 11303
-
biosynthesis of thymidylic acid, only de novo source of thymidine, crucial for DNA replication in every organism
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
Escherichia coli B / ATCC 11303
-
-
-
-
?, r
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
Escherichia coli B / ATCC 11303
-
-
-
-
?, r
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
r
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
biosynthesis of thymidylic acid, only de novo source of thymidine, crucial for DNA replication in every organism
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
biosynthesis of thymidylic acid, only de novo source of thymidine, crucial for DNA replication in every organism
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
r
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
r
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
485382, 485387, 485393, 485398, 485407, 485413, 485426, 485428, 485429, 702996, 703391, 703950, 705044, 706625, 711474, 718866, 719078, 719649, 720965, 720995
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
485359, 485364, 485375, 485376, 485381, 485382, 485384, 485387, 485389, 485393, 485395, 485398, 485400, 485403, 485404, 485407, 485408, 485413, 485415, 485419, 485422, 485423, 485426, 485428, 485429, 485430
-
-
r
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
reverse reaction is at least 630times slower than the forward reaction
-
-
r
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
key function in DNA synthesis, repair and cell division
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
biosynthesis of thymidylic acid, only de novo source of thymidine, crucial for DNA replication in every organism
485358, 485359, 485364, 485375, 485376, 485381, 485384, 485395, 485403, 485404, 485408, 485415, 485423, 485430
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
biosynthesis of thymidylic acid, only de novo source of thymidine, crucial for DNA replication in every organism
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?, r
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
485359, 485360, 485363, 485364, 485365, 485366, 485368, 485369, 485370, 485372, 485376, 485377, 485378, 485379, 485380, 485382, 485383, 485384, 485387, 485388, 485393, 485396, 485397, 485399, 485401, 485403, 485406, 485409, 485410, 485411, 485415, 485416, 485418, 485423, 485427, 485429, 485430, 485431
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
485359, 485360, 485361, 485363, 485364, 485365, 485366, 485368, 485369, 485370, 485372, 485375, 485376, 485377, 485378, 485379, 485380, 485381, 485382, 485383, 485384, 485385, 485387, 485388, 485389, 485393, 485396, 485397, 485399, 485400, 485401, 485403, 485405, 485406, 485409, 485410, 485411, 485415, 485416, 485418, 485419, 485423, 485427, 485429, 485430, 485431
-
-
r
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
key function in DNA synthesis, repair and cell division
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?, r
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
r
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
392255, 485359, 485360, 485363, 485365, 485368, 485369, 485382, 485383, 485384, 485386, 485387, 485390, 485391, 485393, 485398, 485402, 485403, 485413, 485415, 485426, 485427, 485430, 704570
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
392255, 485359, 485360, 485361, 485363, 485365, 485368, 485369, 485373, 485375, 485382, 485383, 485384, 485386, 485387, 485390, 485391, 485393, 485398, 485400, 485402, 485403, 485404, 485413, 485415, 485426, 485427, 485430
-
-
r
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
key function in DNA synthesis, repair and cell division
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
biosynthesis of thymidylic acid, only de novo source of thymidine, crucial for DNA replication in every organism
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
r
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
biosynthesis of thymidylic acid, only de novo source of thymidine, crucial for DNA replication in every organism
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
r
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
key function in DNA synthesis, repair and cell division
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
r
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
r
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
r
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
biosynthesis of thymidylic acid, only de novo source of thymidine, crucial for DNA replication in every organism
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
biosynthesis of thymidylic acid, only de novo source of thymidine, crucial for DNA replication in every organism
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
biosynthesis of thymidylic acid, only de novo source of thymidine, crucial for DNA replication in every organism
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
r
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?, r
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
r
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
r
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?, r
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
r
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
r
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
dUMP substrate binding structure analysis
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?, r
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
r
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?, r
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?, r
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
Trypanosoma rhodesiense
-
-
-
-
?, r
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
tetrahydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
tetrahydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
tetrahydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
tetrahydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + uridine 5'-phosphate
dihydrofolate + TMP
-
-
-
-
r
5,10-methylenetetrahydrofolate + uridine 5'-phosphate
dihydrofolate + TMP
-
-
-
-
r
5,10-methylenetetrahydropteroylheptaglutamate + 2'-deoxyuridylate
7,8-dihydropteroylheptaglutamate + thymidine phosphate
-
-
-
-
r
5,10-methylenetetrahydropteroylheptaglutamate + 2'-deoxyuridylate
7,8-dihydropteroylheptaglutamate + thymidine phosphate
-
-
-
-
r
5,10-methylenetetrahydropteroylpentaglutamate + 2'-deoxyuridylate
7,8-dihydropteroylpentaglutamate + thymidine phosphate
-
-
-
-
r
5,10-methylenetetrahydropteroylpentaglutamate + 2'-deoxyuridylate
7,8-dihydropteroylpentaglutamate + thymidine phosphate
-
-
-
-
r
5-bromo-2'-deoxyuridine 5'-monophosphate + ?
?
-
dehalogenation
-
-
?
5-bromo-2'-deoxyuridine 5'-monophosphate + ?
?
-
dehalogenation does not require methylenetetrahydrofolate as cosubstrate
-
-
?
5-bromo-2'-deoxyuridine 5'-monophosphate + ?
?
-
dehalogenation
-
-
?
5-bromo-2'-deoxyuridine 5'-monophosphate + ?
?
-
dehalogenated by recombinant rat hepatoma enzyme
-
-
?
5-iodo-2'-deoxyuridine 5'-monophosphate + ?
?
-
dehalogenated by recombinant rat hepatoma enzyme
-
-
?
N5,10-methylenetetrahydrofolate + 2'-deoxyuridine 5'-dithiophosphate
7,8-dihydrofolate + ?
-
-
-
-
?
N5,10-methylenetetrahydrofolate + 2'-deoxyuridine 5'-dithiophosphate
7,8-dihydrofolate + ?
-
-
-
-
?
N5,10-methylenetetrahydrofolate + 2'-deoxyuridine 5'-thiophosphate
7,8-dihydrofolate + ?
-
-
-
-
?
N5,10-methylenetetrahydrofolate + 2'-deoxyuridine 5'-thiophosphate
7,8-dihydrofolate + ?
-
-
-
-
?
N5,N10-methylenetetrahydrofolate + dUMP
7,8-dihydrofolate + TMP
-
during thymidylate synthase inhibition, TMP levels decrease with a subsequent increase in dUTP
-
-
?
[6R,S]-5,10-methylenetetrahydropteroylglutamate + 2'-deoxyuridylate
?
-
-
-
-
-
additional information
?
-
-
thymidylate synthase form ThyX has no activity in Corynebacterium glutamicum
-
-
-
additional information
?
-
-
thymidylate synthase form ThyX has no activity in Corynebacterium glutamicum
-
-
-
additional information
?
-
-
the enzyme is specifically bound with its cognate mRNA in vitro and in vivo
-
-
-
additional information
?
-
-
UMP, dCMP and deoxyuridine are no substrates
-
-
-
additional information
?
-
-
nucleotides with large substituents on the 2' position are no substrates
-
-
-
additional information
?
-
-
enzyme catalyzes the exchange of a hydrogen atom between water and position 5 of dUMP, occurrence of reactions other than a methyl-group transfer during the interaction of the enzyme with its 2 substrates
-
-
-
additional information
?
-
-
chemical conversion takes place preferentially via a concerted mechanism where the hydride transfer is conjugated to thiol-elimination from the product. The substrate-enzyme covalent bond established between the C6 of the nucleotide substrate and a conserved cysteine residue is of labile character
-
-
-
additional information
?
-
Escherichia coli B / ATCC 11303
-
nucleotides with large substituents on the 2' position are no substrates
-
-
-
additional information
?
-
Escherichia coli B / ATCC 11303
-
enzyme catalyzes the exchange of a hydrogen atom between water and position 5 of dUMP, occurrence of reactions other than a methyl-group transfer during the interaction of the enzyme with its 2 substrates
-
-
-
additional information
?
-
-
nucleotides with large substituents on the 2' position are no substrates
-
-
-
additional information
?
-
-
enzyme catalyzes the exchange of a hydrogen atom between water and position 5 of dUMP, occurrence of reactions other than a methyl-group transfer during the interaction of the enzyme with its 2 substrates
-
-
-
additional information
?
-
recombinant protein is able to bind its own RNA
-
-
-
additional information
?
-
-
recombinant protein is able to bind its own RNA
-
-
-
additional information
?
-
-
inhibitors targeted at human TS designed from structures of bacterial TS may not be optimal
-
-
-
additional information
?
-
-
dCMP is no substrate, exception mutant TS N229D
-
-
-
additional information
?
-
-
dCMP is no substrate, exception mutant TS N229D
-
-
-
additional information
?
-
-
bifunctional enzyme dihydrofolate reductase-thymidylate synthase
-
-
-
additional information
?
-
-
bifunctional enzyme dihydrofolate reductase-thymidylate synthase
-
-
-
additional information
?
-
-
bifunctional enzyme dihydrofolate reductase-thymidylate synthase
-
-
-
additional information
?
-
-
bifunctional enzyme dihydrofolate reductase-thymidylate synthase
-
-
-
additional information
?
-
-
bifunctional enzyme dihydrofolate reductase-thymidylate synthase
-
-
-
additional information
?
-
-
uridylate, cytidylate and deoxycytidylate are not substrates
-
-
-
additional information
?
-
-
bifunctional enzyme thymidilate synthase-dihydrofolate reductase, not possible to separate the 2 activities
-
-
-
additional information
?
-
-
bifunctional enzyme dihydrofolate reductase-thymidylate synthase
-
-
-
additional information
?
-
-
bifunctional enzyme dihydrofolate reductase-thymidylate synthase
-
-
-
additional information
?
-
molecular mechanism of the distinct differences in substrate channeling behavior between Toxoplasma gondii TS-DHFR and Cryptosporidium hominis TS-DHFR, overview
-
-
-
additional information
?
-
the bifunctional folate and pyrimidine-metabolising enzyme dihydrofolate reductase-thymidylate synthase dihydrofolate reductase-thymidylate synthase is expressed from a single gene as a homodimer comprising of an N-terminal DHFR domain fused via a linker peptide to a thymidylate synthase domain at the C-terminus
-
-
-
additional information
?
-
no activity with folic acid and the structurally related pterins (biopterin, dihydrobiopterin, sepiapterin and neopterin) as substrates by enzyme DHFR-TS
-
-
-
additional information
?
-
the bifunctional folate and pyrimidine-metabolising enzyme dihydrofolate reductase-thymidylate synthase dihydrofolate reductase-thymidylate synthase is expressed from a single gene as a homodimer comprising of an N-terminal DHFR domain fused via a linker peptide to a thymidylate synthase domain at the C-terminus
-
-
-
additional information
?
-
no activity with folic acid and the structurally related pterins (biopterin, dihydrobiopterin, sepiapterin and neopterin) as substrates by enzyme DHFR-TS
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
5,10-methylene-5,6,7,8-tetrahydrofolate + dUMP
7,8-dihydrofolate + dTMP
-
thymidylate synthase is the third enzyme in the methylene tetrahydrofolate cycle besides dihydrofolate reductase and serine hydroxymethyltransferase, in many organisms, thymidylate synthase is the only de novo source for dTMP required for DNA synthesis
-
-
?
5,10-methylenetetrahydrofolate + deoxyuridine monophosphate
7,8-dihydrofolate + deoxythymidine monophosphate
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
7,8-dihydrofolate + TMP
-
during TS inhibition, TMP levels decrease with a subsequent increase in dUTP
-
-
?
N5,N10-methylenetetrahydrofolate + dUMP
7,8-dihydrofolate + TMP
-
during thymidylate synthase inhibition, TMP levels decrease with a subsequent increase in dUTP
-
-
?
5,10-methylenetetrahydrofolate + dUMP
7,8-dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
7,8-dihydrofolate + dTMP
thymidylate synthase is essential for de novo synthesis of dTMP and is a key enzyme involved in DNA synthesis and transcriptional regulation of organisms
-
-
?
5,10-methylenetetrahydrofolate + dUMP
7,8-dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
7,8-dihydrofolate + dTMP
-
inhibition of thymidylate synthase or of DHFR leads to thymineless death of eukaryotic organisms
-
-
?
5,10-methylenetetrahydrofolate + dUMP
7,8-dihydrofolate + dTMP
-
it is a key enzyme for the synthesis of the DNA-specific nucleotide thymidylate
-
-
?
5,10-methylenetetrahydrofolate + dUMP
7,8-dihydrofolate + dTMP
-
thymidylate synthase catalyses the only de novo pathway to produce thymidylate for DNA replication and repair
-
-
?
5,10-methylenetetrahydrofolate + dUMP
7,8-dihydrofolate + dTMP
-
thymidylate synthase is a key enzyme in the de novo synthesis of dTMP
-
-
?
5,10-methylenetetrahydrofolate + dUMP
7,8-dihydrofolate + dTMP
-
TS is a key enzyme in folate metabolism
-
-
?
5,10-methylenetetrahydrofolate + dUMP
7,8-dihydrofolate + dTMP
-
thymidylate synthase is an essential enzyme for de novo synthesis of thymidylate (dTMP), a precursor for DNA synthesis
-
-
?
5,10-methylenetetrahydrofolate + dUMP
7,8-dihydrofolate + dTMP
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
key function in DNA synthesis, repair and cell division
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
biosynthesis of thymidylic acid, only de novo source of thymidine, crucial for DNA replication in every organism
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
biosynthesis of thymidylic acid, only de novo source of thymidine, crucial for DNA replication in every organism
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
biosynthesis of thymidylic acid, only de novo source of thymidine, crucial for DNA replication in every organism
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
key function in DNA synthesis, repair and cell division
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
biosynthesis of thymidylic acid, only de novo source of thymidine, crucial for DNA replication in every organism
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
485357, 485363, 485365, 485369, 485371, 485372, 485374, 485382, 485383, 485388, 485397, 485402, 485406, 485409, 485413, 485416, 485417
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
key function in DNA synthesis, repair and cell division
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
biosynthesis of thymidylic acid, only de novo source of thymidine, crucial for DNA replication in every organism
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
Escherichia coli B / ATCC 11303
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
Escherichia coli B / ATCC 11303
-
key function in DNA synthesis, repair and cell division
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
Escherichia coli B / ATCC 11303
-
biosynthesis of thymidylic acid, only de novo source of thymidine, crucial for DNA replication in every organism
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
Escherichia coli B / ATCC 11303
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
biosynthesis of thymidylic acid, only de novo source of thymidine, crucial for DNA replication in every organism
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
biosynthesis of thymidylic acid, only de novo source of thymidine, crucial for DNA replication in every organism
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
key function in DNA synthesis, repair and cell division
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
biosynthesis of thymidylic acid, only de novo source of thymidine, crucial for DNA replication in every organism
485358, 485359, 485364, 485375, 485376, 485381, 485384, 485395, 485403, 485404, 485408, 485415, 485423, 485430
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
biosynthesis of thymidylic acid, only de novo source of thymidine, crucial for DNA replication in every organism
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
485359, 485360, 485363, 485364, 485365, 485366, 485368, 485369, 485370, 485372, 485376, 485377, 485378, 485379, 485380, 485382, 485383, 485384, 485387, 485388, 485393, 485396, 485397, 485399, 485401, 485403, 485406, 485409, 485410, 485411, 485415, 485416, 485418, 485423, 485427, 485429, 485430, 485431
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
key function in DNA synthesis, repair and cell division
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
392255, 485359, 485360, 485363, 485365, 485368, 485369, 485382, 485383, 485384, 485386, 485387, 485390, 485391, 485393, 485398, 485402, 485403, 485413, 485415, 485426, 485427, 485430
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
key function in DNA synthesis, repair and cell division
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
biosynthesis of thymidylic acid, only de novo source of thymidine, crucial for DNA replication in every organism
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
biosynthesis of thymidylic acid, only de novo source of thymidine, crucial for DNA replication in every organism
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
key function in DNA synthesis, repair and cell division
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
biosynthesis of thymidylic acid, only de novo source of thymidine, crucial for DNA replication in every organism
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
biosynthesis of thymidylic acid, only de novo source of thymidine, crucial for DNA replication in every organism
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
biosynthesis of thymidylic acid, only de novo source of thymidine, crucial for DNA replication in every organism
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
?
additional information
?
-
recombinant protein is able to bind its own RNA
-
-
-
additional information
?
-
-
recombinant protein is able to bind its own RNA
-
-
-
additional information
?
-
the bifunctional folate and pyrimidine-metabolising enzyme dihydrofolate reductase-thymidylate synthase dihydrofolate reductase-thymidylate synthase is expressed from a single gene as a homodimer comprising of an N-terminal DHFR domain fused via a linker peptide to a thymidylate synthase domain at the C-terminus
-
-
-
additional information
?
-
the bifunctional folate and pyrimidine-metabolising enzyme dihydrofolate reductase-thymidylate synthase dihydrofolate reductase-thymidylate synthase is expressed from a single gene as a homodimer comprising of an N-terminal DHFR domain fused via a linker peptide to a thymidylate synthase domain at the C-terminus
-
-
-
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
N5,N10-methylenetetrahydrofolate
-
-
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
KCl
the optimal ionic strength for both enzymes requires 100 mM KCl, with DHFR displaying 2.5fold activation and TS 4.5fold activation
Mg2+
Mg2+
-
in Tris-acetate buffers 10 mM enhances enzyme activity by some 30%
Mg2+
TS is activated 4.5fold at 10 mM MgCl2, but inhibited at higher concentrations of MgCl2. The activating effect is not additive with activation by KCl
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(2S)-2-[(4-([(2,4-diaminopteridin-6-yl)methyl](methyl)amino)phenyl)formamido]pentanedioic acid
i.e, methotrexate, A DHFR inhibitor, binds at the DHFR active site
(2S)-2-[([4-[(2-amino-6-methyl-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)sulfanyl]phenyl]carbonyl)amino]pentanedioic acid
(S)-2-(5(((1,2-dihydro-3-methyl-1-oxobenzo(f)quinazolin-9-yl)methyl)amino)1-oxo-2-isoindolinyl)glutaric acid
-
BW1843U89, U89, distorts the thymidylate synthase active site
(S)-2-(5(((1,2-dihydro-3-methyl-1-oxobenzo[f]quinazolin-9 yl)methyl)amino)1-oxo-2-isoindolinyl)glutaric acid
-
(S)-2-(5(((1,2-dihydro-3-methyl-1-oxobenzo[f]quinazolin-9-yl)methyl)amino)1-oxo-2-isoindolinyl)glutaric acid
-
(S)-2-(5-(((1,2-dihydro3-methyl-1-oxobenzo[f]quinazolin-9-yl)methyl)amino)-1-oxo-2-isoindolinyl)glutaric acid
-
BW1843U89
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
1-(beta-D-2'-deoxyribofuranosyl)1,6-dihydro-8-azapurin-2(3H,6H)-one 5'-monophosphate
-
-
1-(beta-D-2-deoxyribofuranosyl)-4-hydroxyamino-5-bromopyrimidin-2(1H)-one 5'-monophosphate
-
-
1-(beta-D-2-deoxyribofuranosyl)-4-hydroxyamino-5-chloropyrimidin-2(1H)-one 5'-monophosphate
-
-
1-(beta-D-2-deoxyribofuranosyl)-4-hydroxyamino-5-fluoropyrimidin-2(1H)-one 5'-monophosphate
-
-
1-(beta-D-2-deoxyribofuranosyl)-4-hydroxyamino-5-hydroxymethylpyrimidin-2(1H)-one 5'-monophosphate
-
-
1-(beta-D-2-deoxyribofuranosyl)-4-hydroxyamino-5-iodopyrimidin-2(1H)-one 5'-monophosphate
-
-
1-(beta-D-2-deoxyribofuranosyl)-4-hydroxyaminopyrimidin-2(1H)-one 5'-monophosphate
-
-
1843U89
i.e. (2R)-2-(5-[[(1-hydroxy-3-methyl-5,10a-dihydrobenzo[f]quinazolin-9-yl)methyl]amino]-1-oxo-1,3-dihydro-2H-isoindol-2-yl)butanedioic acid, folate-based inhibitor
2'-deoxy-2',2'-difluorouridine 5'-dihydrogen
-
classic inhibitor (no time dependence of inhibition observed)
2'-fluoro-ara-UMP
-
classic inhibitor (no time dependence of inhibition observed)
3,3-bis(4-methoxyphenyl)-1H,3H-benzo[de]isochromen-1-one
-
induces apoptotic cell death in SK-MEL-2 and SK-MEL-28 melanoma cell lines, mediated by downregulation of Bcl-2 protein level and PARP cleavage, and independent of p53 and Bax. Pan-caspases inhibitor Z-VAD-FMK blocks the effect
5'-CGCGGTACGGACACCGCGCG-3'
-
targets the TS mRNA translation start site TSS and increases the thymidylate synthase gene transcription in HeLa cell
-
5-fluoro-2'-deoxyuridine
-
comparison with inhibitory effect of FdUMP[10] and 5-fluorouraci
5-fluoro-dUMP[10]
-
a 10-mer of 5-fluoro-dUMP, a suicide inhibitor of thymidylate synthase, designed to bypass resistance to 5-fluorouracil, acts as a pro-drug of 5-fluoro-dUMP
6-bromo-3,3-bis(3-chloro-4-hydroxyphenyl)-1H,3H-benzo[de]isochromen-1-one
-
induces apoptotic cell death in SK-MEL-2 and SK-MEL-28 melanoma cell lines, mediated by downregulation of Bcl-2 protein level and PARP cleavage, and independent of p53 and Bax. Pan-caspases inhibitor Z-VAD-FMK blocks the effect
6-chloro-3,3-bis(4-hydroxyphenyl)-1H,3H-benzo[de]isochromen-1-one
-
induces apoptotic cell death in SK-MEL-2 and SK-MEL-28 melanoma cell lines, mediated by downregulation of Bcl-2 protein level and PARP cleavage, and independent of p53 and Bax. Pan-caspases inhibitor Z-VAD-FMK blocks the effect
BGC 9331
-
treatment results in concentration-dependent increase in thymidine uptake in FR-positive epidermoid KB cells and in increase of membrane-associated equilibrative nucleoside transporter type 1 levels. Tumor [18F]-fluorothymidine accumulation in KB xenografts increases by more than 2fold with maximal levels at 1 to 4 hours and 4 to 24 hours after drug treatment. Quantitiative changes in tumor [18F]-fluorothymidine uptake are associated with increased tumor dUrd levels. BGC 9331 induces accumulation of [18F]-fluorothymidine uptake in the intestine
BGC 945
-
alpha-folate receptor targeted antifolate TS inhibitor; cyclopenta[g]quinazoline-based inhibitor. Treatment results in concentration-dependent increase in thymidine uptake in FR-positive epidermoid KB cells and in increase of membrane-associated equilibrative nucleoside transporter type 1 levels. Tumor [18F]-fluorothymidine accumulation in KB xenografts increases by more than 2fold with maximal levels at 1 to 4 hours and 4 to 24 hours after drug treatment. Quantitiative changes in tumor [18F]-fluorothymidine uptake are associated with increased tumor dUrd levels
FdUMP[10]
-
multimer of 5-fluoro-2'-deoxyuridine 5'-monophosphate, inhibits cell growth with greater potency than 5-fluorouracil and 5-fluoro-2'-deoxyuridine
gefitinib
-
inhibits the expression of the transcription factor E2F-1, resulting in a down-regulation of thymidylate synthase at the mRNA and protein level; inhibits the expression of the transcription factor E2F-1, resulting in the down-regulation of thymidylate synthase at the mRNA and protein levels
Hydroxyurea
-
supresses thymidilate synthase in growing algae, but no effect on purified enzyme
LSCQLYQR
-
octapeptide to specifically target the monomer-monomer interface of the enzyme. A fast-equilibrium mechanism exists that combines trafficking in/out of the cell and degradation pathways within cells
N-(4-((2-amino-6-methyl-4-oxo-3,4-dihydro-5H-pyrrolo(3,2-d)pyrimidin-5-yl)methyl)benzoyl)-L-glutamic acid
N-(4-((2-amino-6-methyl-4-oxo-3,4-dihydrothieno(2,3-d)pyrimidin-5-yl)sulfanyl)benzoyl)-L-glutamic acid
-
-
N-(4-((2-amino-6-methyl-4-oxo-4,7-dihydro-3H-pyrrolo(2,3-d)pyrimidin-5-yl)thio)benzoyl)-L-glutamic acid
N-(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]benzoyl)-gamma-glutamyl-gamma-glutamyl-gamma-glutamyl-gamma-glutamylglutamic acid
-
-
N-(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]benzoyl)-gamma-glutamyl-gamma-glutamylglutamic acid
-
-
N-(4-{[(2-amino-4-oxo-1,4-dihydroquinazolin-6-yl)methyl](prop-2-ynoyl)amino}benzoyl)-L-glutamic acid
-
-
N-([5-[2-(2,4-diaminoquinazolin-6-yl)ethyl]-2,3-dihydrothiophen-2-yl]carbonyl)-4-methylideneglutamic acid
-
-
N-[4-[(2-amino-6-ethyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-5-yl)thio]benzoyl]-L-glutamic acid
N-[4-[(2-amino-6-methyl-4-oxo-3,4-dihydro-5H-pyrrolo[3,2-d]pyrimidin-5-yl)methyl]benzoyl]-L-glutamic acid
N-[4-[(2-amino-6-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-5-yl)sulfanyl]benzoyl]-L-glutamic acid
N-[4-[2-(2,4-diamino-7H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-4-methylideneglutamic acid
-
-
N-[4-[2-(2,4-diaminopyrido[3,2-d]pyrimidin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid
-
-
N-[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]-2-fluorobenzoyl]-4-methylideneglutamic acid
-
-
N-[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid
-
-
N-[4-[2-(2-amino-4-methylquinazolin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid
-
-
N10-propargyl-5,8-dideazafolate
PDDF, a TS folate inhibitor, binds at the TS active site. Residues that are involved in binding the folate analogue PDDF include I402, D513, L516, F520, as well as the nonconserved R603 and conserved M608 located on the C-terminal tail of the TS-domain
novobiocin
-
coumarin antibiotic produced by Streptomyces nivens, at 10 mM concentration the self-splicing of primary transcripts is inhibited by about 5%, at 40 mM concentration the splicing rate is inhibited by about 50%. The splicing inhibition is strongly dependent on Mg2+
OSI-7904L
-
a liposomal thymidylate synthase inhibitor, a liposomal formulation of OSI-7904 (S)-2-(5-((1,2-dihydro-3-methyl-1-oxobenzo(f)quinazolin-9-yl)methyl)amino-1-oxo-2-isoindolynl)-glutaric acid, administered in combination with oxaliplatin every 21 days in patients with advanced colorectal carcinoma; treatment of patients with advanced colorectal carcinoma, in combination with oxaliplatin. At the highest dose level of OSI-7904L 9 mg/m2, oxaliplatin 130 mg/m2, one of nine patients experienced dose-limiting toxicity of grade 3 oral mucositis with cycle 1 and five further patients required dose reductions. The toxicity profile of stomatitis, diarrhea, nausea, fatigue, sensory neuropathy and skin rash was consistent with that expected for a thymidylate synthase inhibitor/oxaliplatin combination regimen. High interpatient variability with no detectable interaction between OSI-7904L and oxaliplatin
propylene diphosphonate
-
mixed competitive-noncompetitive inhibitor with respect to dUMP
ZD9331
-
antifolate inhibitor, shows positive cooperativity with 1,3-propanediphosphonic acid
(2S)-2-[([4-[(2-amino-6-methyl-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)sulfanyl]phenyl]carbonyl)amino]pentanedioic acid
-
dual inhibitor of thymidylate synthase and dihydrofolate reductase. Comparison with inhibitory effect on human and Toxoplasma gondii enzyme
(2S)-2-[([4-[(2-amino-6-methyl-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)sulfanyl]phenyl]carbonyl)amino]pentanedioic acid
-
dual inhibitor of thymidylate synthase and dihydrofolate reductase. Comparison with inhibitory effect on Escherichia coli and Toxoplasma gondii enzyme
1,1-bis-(4-hydroxyphenyl)-1H-naphtho[1,2-c]furan-3-one