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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
- ribonucleotide
-
resect
- fdump
- pemetrexed
- leucovorin
-
5-fu-based
-
non-small
-
casey
- polyglutamates
- uracil
- cisplatin
- mthfr
- irinotecan
- folylpolyglutamate
- deoxyuridine
- 5-fluoro-2'-deoxyuridine
-
antimetabolite
- oxaliplatin
- capecitabine
- orotate
-
tegafur
- medicine
- gemcitabine
-
formyltransferase
- glycinamide
- dttp
- quinazoline
- 2'-deoxyuridine
-
folinic
-
polyglutamylation
-
folate-dependent
-
ccrf-cem
- aminopterin
-
5-fu-induced
- drug development
-
cross-complementing
- mucositis
- dutpase
-
methotrexate-resistant
- deoxycytidylate
- deoxythymidine
-
transformylase
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
-
-
-
-
HTS
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 synthase-dihydrofolate reductase
bifunctional enzyme
thymidylate synthase-dihydrofolate reductase
bifunctional enzyme
-
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
dTMP de novo biosynthesis (mitochondrial), 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
-
-
-
?
(R)-5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
?
5,10-methylene-5,6,7,8-tetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
-
r
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
methylenetetrahydropteroylglutamate + dUMP
7,8-dihydropteroylglutamate + thymidine phosphate
-
-
-
r
N5,10-methylenetetrahydrofolate + 2'-deoxyuridine 5'-dithiophosphate
7,8-dihydrofolate + ?
N5,10-methylenetetrahydrofolate + 5-hydroxy-2'-deoxyuridine 5'-monophosphate
7,8-dihydrofolate + ?
-
-
-
-
?
[6R]methylenetetrahydropteroyldiglutamate + dUMP
7,8-dihydropteroyldiglutamate + thymidine phosphate
-
-
-
-
r
[6R]methylenetetrahydropteroylheptaglutamate + dUMP
7,8-dihydropteroylheptaglutamate + thymidine phosphate
-
-
-
-
r
[6R]methylenetetrahydropteroylhexaglutamate + dUMP
7,8-dihydropteroylhexaglutamate + thymidine phosphate
-
-
-
-
r
[6R]methylenetetrahydropteroylpentaglutamate + dUMP
7,8-dihydropteroylpentaglutamate + thymidine phosphate
-
-
-
-
r
[6R]methylenetetrahydropteroyltetraglutamate + dUMP
7,8-dihydropteroyltetraglutamate + thymidine phosphate
-
-
-
-
r
[6R]methylenetetrahydropteroyltriglutamate + dUMP
7,8-dihydropteroyltriglutamate + thymidine phosphate
-
-
-
-
r
(-)-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
-
-
-
-
?
(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
-
-
-
-
?
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-methylenetetrahydrofolate + 2'-deoxycytidine 5'-monophosphate
dihydrofolate + cytidine phosphate
-
only mutant TS N229D
-
-
?
5,10-methylenetetrahydrofolate + 2'-deoxycytidine 5'-monophosphate
dihydrofolate + cytidine phosphate
Lacticaseibacillus casei TS N229D
-
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
-
-
-
?
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
-
-
-
-
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
-
-
-
?
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
-
-
-
-
?
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, 485421, 485425, 705044, 705333, 706772, 711474, 757061
-
-
?
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, 485419, 485421, 485422, 485423, 485425, 485430, 485431
-
-
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
-
-
-
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, 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
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
-
-
-
?
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
Lacticaseibacillus casei TS N229D
-
-
-
-
?, 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
-
-
-
-
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
-
-
-
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
-
-
-
-
?
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
-
-
-
?
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 + 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
?
-
Lacticaseibacillus casei TS N229D
-
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
?
-
-
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
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, 485421, 485425
-
-
?
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
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
Lacticaseibacillus casei TS N229D
-
-
-
-
?
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
-
-
-
-
?
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
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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+
additional information
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
additional information
presence of Mg2+ does not enhance reaction rates and has no impact on the transition state structure of hydride transfer
additional information
-
presence of Mg2+ does not enhance reaction rates and has no impact on the transition state structure of hydride transfer
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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-(5-cyano-1,6-dihydro-6-oxo-4-p-tolylpyrimidin-2-yl)-4-phenylthiosemicarbazide
-
1-(beta-D-2'-deoxyribofuranosyl)1,6-dihydro-8-azapurin-2(3H,6H)-one 5'-monophosphate
-
-
1-(beta-D-2'-Deoxyribofuranosyl)8-azapurin-2-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)
2,4-dioxo-N-(2-(1-(m-tolyl)-1H-1,2,3-triazol-4-yl)phenyl)-1, 2, 3, 4-tetrahydropyrimidine-5-sulfonamide
-
2-(2-(4-((2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)methyl)benzamido)-4-cyanophenyl)acetic acid
-
2-(2-(4-((2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)methyl)benzamido)-4-methoxyphenyl)acetic acid
-
2-(2-(4-((2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)methyl)benzamido)phenyl) acetic acid
-
2-(2-(4-hydroxybenzylidene)hydrazinyl)-6-oxo-4-(p-tolyl)-1,6-dihydropyrimidine-5-carbonitrile
-
2-(4-((2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)methyl)benzamido) terephthalic acid
-
2-(4-((2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)methyl)benzamido)-4-chloro benzoic acid
-
2-(4-((2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)methyl)benzamido)-4-cyanobenzoic acid
-
2-(4-hydroxy[1,1'-biphenyl]-3-yl)-4-methyl-1H-isoindole-1,3(2H)-dione
-
2-chloro-N'-[5-methyl-4-(4-methylphenyl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetohydrazide
-
2-[2-(3-methoxyphenoxy)propyl]-4-methyl-1H-isoindole-1,3(2H)-dione
-
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
3-(4-((2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)methyl)benzamido)-4-(carboxymethyl)benzoic acid
-
3-beta-D-ribofuranosylmaleimide 5'-phosphate
-
showdomycin 5'-phosphate
4'-[(4-methyl-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl][1,1'-biphenyl]-2-carbonitrile
-
4,5,6,7-tetrachloro-2-[3-(phenylsulfanyl)propyl]-1H-isoindole-1,3(2H)-dione
-
4-chloro-N'-(5-cyano-1,6-dihydro-6-oxo-4-p-tolylpyrimidin-2-yl)benzohydrazide
-
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
CQLYQRSG
allosteric peptide inhibitor, binds to the dimer interface and stabilizes the inactive form of the protein
-
crocetin
binding pattern of crocetin is similar to that of ralitrexed and it poses maximum MolDock score as well as the rerank score
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
LCQFYVVN
allosteric peptide inhibitor, binds to the dimer interface and stabilizes the inactive form of the protein
-
N',N'-diacetyl-N-(5-cyano-1,6-dihydro-6-oxo-4-p-tolylpyrimidin-2-yl)acetohydrazide
compound induces the level of active caspase 3, and elevates the Bax/Bcl2 ratio 44fold in comparison to the control
N'-(3-chlorobenzoyl)-2-(2,4-dihydroxypyrimidine-5-sulfonamido)benzoyl hydrazide
IC50 value 0.00126 mM for A-549 cells, 0.00208 mM for OVCAR-3 cells, 0.00182 mM for SCG-7901 cells, 0.00442 mM for MDA-MB-231 cells