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Information on EC 2.1.1.45 - thymidylate synthase and Organism(s) Homo sapiens and UniProt Accession P04818

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EC Tree
     2 Transferases
         2.1 Transferring one-carbon groups
             2.1.1 Methyltransferases
                2.1.1.45 thymidylate synthase
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Homo sapiens
UNIPROT: P04818 not found.
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Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
Synonyms
thymidylate synthase, thymidylate synthetase, human ts, dtmp synthase, thymidylate synthase a, tmp synthetase, y110a7a.4, 5,10-methylenetetrahydrofolate:dump c-methyltransferase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dTMP synthase
-
-
-
-
human TS
-
-
methylenetetrahydrofolate:dUMP C-methyltransferase
-
-
-
-
thymidylate synthase
-
-
thymidylate synthetase
TMP synthetase
-
-
-
-
TMPS
-
-
TS-DHFR
-
-
TSase
-
-
TYMS
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
reductive methylation
-
dehalogenation
-
-
-
-
methylene group transfer
-
-
-
-
reductive methylation
PATHWAY SOURCE
PATHWAYS
-
-, -, -, -, -, -, -, -, -
SYSTEMATIC NAME
IUBMB Comments
5,10-methylenetetrahydrofolate:dUMP C-methyltransferase
-
CAS REGISTRY NUMBER
COMMENTARY hide
9031-61-2
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(6R)-N5,N10-methylene-5,6,7,8-tetrahydrofolate + 2'-deoxyuridylate
7,8-dihydrofolate + 5-methyl-2'-deoxyuridylate
show the reaction diagram
-
-
-
r
5,10-methylenetetrahydrofolate + dUMP
7,8-dihydrofolate + dTMP
show the reaction diagram
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
show the reaction diagram
5,10-methylene-5,6,7,8-tetrahydrofolate + dUMP
7,8-dihydrofolate + dTMP
show the reaction diagram
-
-
-
-
?
5,10-methylenetetrahydrofolate + 6-fluoro-dUMP
?
show the reaction diagram
-
-
-
-
?
5,10-methylenetetrahydrofolate + dUMP
7,8-dihydrofolate + dTMP
show the reaction diagram
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
show the reaction diagram
5,10-methylenetetrahydropteroylheptaglutamate + 2'-deoxyuridylate
7,8-dihydropteroylheptaglutamate + thymidine phosphate
show the reaction diagram
-
-
-
-
r
5,10-methylenetetrahydropteroylpentaglutamate + 2'-deoxyuridylate
7,8-dihydropteroylpentaglutamate + thymidine phosphate
show the reaction diagram
-
-
-
-
r
N5,10-methylenetetrahydrofolate + 5-hydroxy-2'-deoxyuridine 5'-monophosphate
7,8-dihydrofolate + ?
show the reaction diagram
-
-
-
-
?
N5,N10-methylenetetrahydrofolate + dUMP
7,8-dihydrofolate + TMP
show the reaction diagram
[6R]-methylenetetrahydropteroylglutamate + 2'-deoxyuridylate
?
show the reaction diagram
-
-
-
-
r
[6R]methylenetetrahydropteroyldiglutamate + dUMP
7,8-dihydropteroyldiglutamate + thymidine phosphate
show the reaction diagram
-
-
-
-
r
[6R]methylenetetrahydropteroylheptaglutamate + dUMP
7,8-dihydropteroylheptaglutamate + thymidine phosphate
show the reaction diagram
-
-
-
-
r
[6R]methylenetetrahydropteroylhexaglutamate + dUMP
7,8-dihydropteroylhexaglutamate + thymidine phosphate
show the reaction diagram
-
-
-
-
r
[6R]methylenetetrahydropteroylpentaglutamate + dUMP
7,8-dihydropteroylpentaglutamate + thymidine phosphate
show the reaction diagram
-
-
-
-
r
[6R]methylenetetrahydropteroyltetraglutamate + dUMP
7,8-dihydropteroyltetraglutamate + thymidine phosphate
show the reaction diagram
-
-
-
-
r
[6R]methylenetetrahydropteroyltriglutamate + dUMP
7,8-dihydropteroyltriglutamate + thymidine phosphate
show the reaction diagram
-
-
-
-
r
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
5,10-methylenetetrahydrofolate + dUMP
7,8-dihydrofolate + dTMP
show the reaction diagram
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
show the reaction diagram
5,10-methylenetetrahydrofolate + dUMP
7,8-dihydrofolate + dTMP
show the reaction diagram
5,10-methylenetetrahydrofolate + dUMP
dihydrofolate + dTMP
show the reaction diagram
N5,N10-methylenetetrahydrofolate + dUMP
7,8-dihydrofolate + TMP
show the reaction diagram
-
during thymidylate synthase inhibition, TMP levels decrease with a subsequent increase in dUTP
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
N5,N10-methylenetetrahydrofolate
-
methenyltetrahydrofolate
-
-
methylenetetrahydrofolate
-
-
N5,N10-methylenetetrahydrofolate
-
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1,3-propanediphosphonic acid
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
-
10-propargyl-5,8-dideazafolate
i.e. PDDF. Dual inhibitor of thymidylate synthase and dihydrofolate reductase. Comparison with inhibitory effect on Escherichia coli and Toxoplasma gondii enzyme
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-hydroxybenzylidene)hydrazinyl)-6-oxo-4-(p-tolyl)-1,6-dihydropyrimidine-5-carbonitrile
-
2-amino-5-[(3,4-dichlorophenyl)sulfanyl]-6-methylthieno[2,3-d]pyrimidin-4(3H)-one
dual inhibitor of thymidylate synthase and dihydrofolate reductase. Comparison with inhibitory effect on Escherichia coli and Toxoplasma gondii enzyme
2-amino-6-methyl-5-(2-naphthylsulfanyl)thieno[2,3-d]pyrimidin-4(3H)-one
dual inhibitor of thymidylate synthase and dihydrofolate reductase. Comparison with inhibitory effect on Escherichia coli and Toxoplasma gondii enzyme
2-amino-6-methyl-5-[(4-nitrophenyl)sulfanyl]thieno[2,3-d]pyrimidin-4(3H)-one
dual inhibitor of thymidylate synthase and dihydrofolate reductase. Comparison with inhibitory effect on Escherichia coli and Toxoplasma gondii enzyme
2-chloro-N'-[5-methyl-4-(4-methylphenyl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetohydrazide
-
2-hydrazinyl-1,6-dihydro-6-oxo-4-p-tolyl pyrimidine-5-carbonitrile
-
4-chloro-N'-(5-cyano-1,6-dihydro-6-oxo-4-p-tolylpyrimidin-2-yl)benzohydrazide
-
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
LCQFYVVN
allosteric peptide inhibitor, binds to the dimer interface and stabilizes the inactive form of the protein
LSCQLYQR
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
N'-(5-cyano-1,6-dihydro-6-oxo-4-p-tolylpyrimidin-2-yl)-4-nitrobenzohydrazide
-
N'-(5-cyano-1,6-dihydro-6-oxo-4-p-tolylpyrimidin-2-yl)benzohydrazide
-
N-(2-(1-(2-chlorophenyl)-1H-1,2,3-triazol-4-yl) phenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-sulfonamide
-
N-(2-(1-(3-chlorophenyl)-1H-1,2,3-triazol-4-yl) phenyl)-2,4-dioxo-1, 2,3,4-tetrahydropyrimidine-5-sulfonamide
-
N-(2-(1-(4-chlorophenyl)-1H-1,2,3-triazol-4-yl) phenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-sulfonamide
compound exhibits the most potent activity against A-549 cells (IC50 1.18 microM) and prominent enzyme inhibition. It inhibits A-549 cells proliferation by arresting the cell cycle in the G1/S phase. The inhibitor can downregulate the cycle checkpoint proteins cyclin D1 and cyclin E to inhibit the cell cycle progression, and then induce intrinsic apoptosis by activating caspase-3, and reducing the ratio of bcl-2/bax
N-(3-(1-(2-chlorophenyl)-1H-1,2,3-triazol-4-yl) phenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-sulfonamide
-
N-(3-(1-(3-chlorophenyl)-1H-1,2,3-triazol-4-yl) phenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-sulfonamide
-
N-(3-(1-(4-chlorophenyl)-1H-1,2,3-triazol-4-yl) phenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-sulfonamide
-
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-(1-(2-chlorophenyl)-1H-1,2,3-triazol-4-yl) phenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-sulfonamide
-
N-(4-(1-(3-chlorophenyl)-1H-1,2,3-triazol-4-yl) phenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-sulfonamide
-
N-(4-(1-(4-chlorophenyl)-1H-1,2,3-triazol-4-yl) phenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-sulfonamide
-
N-[4-[(2-amino-6-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-5-yl)sulfanyl]benzoyl]-L-glutamic acid
dual inhibitor of thymidylate synthase and dihydrofolate reductase. Comparison with inhibitory effect on Escherichia coli and Toxoplasma gondii enzyme
niazimicin
-
nolatrexed
upon binding, the two insert regions in thymidylate synthase, the functions of which are unclear, undergo positional shifts toward the catalytic center
pemetrexed
dual inhibitor of thymidylate synthase and dihydrofolate reductase. Comparison with inhibitory effect on Escherichia coli and Toxoplasma gondii enzyme
pentalongin
-
picrocrocin
-
QFYVVNSE
allosteric peptide inhibitor, binds to the dimer interface and stabilizes the inactive form of the protein
ralitrexed
-
raltitrexed
upon binding, the two insert regions in thymidylate synthase, the functions of which are unclear, undergo positional shifts toward the catalytic center
scopoletin
-
SELSCQLY
allosteric peptide inhibitor, binds to the dimer interface and stabilizes the inactive form of the protein
turmerone
-
VNSELSCQ
allosteric peptide inhibitor, binds to the dimer interface and stabilizes the inactive form of the protein
YVVNSELS
allosteric peptide inhibitor, binds to the dimer interface and stabilizes the inactive form of the protein
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 Escherichia coli and Toxoplasma gondii enzyme
(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
10-formyl-7,8 dihydrofolate-tetra-gamma-L-glutamate
-
-
10-formyldihydropteroylpentaglutamate
-
-
10-propargyl-5,8-dideazafolate
2-amino-5-[(2,5-dimethoxyphenyl)sulfanyl]-6-ethylthieno[2,3-d]pyrimidin-4(3H)-one
-
-
2-amino-5-[(2-chlorophenyl)sulfanyl]-6-ethylthieno[2,3-d]pyrimidin-4(3H)-one
-
-
2-amino-5-[(3,4-dichlorophenyl)thio]-6-ethylthieno[2,3-d]pyrimidin-4(3H)-one
-
-
2-amino-5-[(3,5-dichlorophenyl)sulfanyl]-6-ethylthieno[2,3-d]-pyrimidin-4(3H)-one
-
-
2-amino-5-[(3,5-dimethoxyphenyl)sulfanyl]-6-ethylthieno[2,3-d]pyrimidin-4(3H)-one
-
-
2-amino-5-[(3-chlorophenyl)sulfanyl]-6-ethylthieno[2,3-d]pyrimidin-4(3H)-one
-
-
2-amino-5-[(4-bromophenyl)sulfanyl]-6-ethylthieno[2,3-d]pyrimidin-4(3H)-one
-
-
2-amino-5-[(4-chlorophenyl)sulfanyl]-6-ethylthieno[2,3-d]pyrimidin-4(3H)-one
-
-
2-amino-6-ethyl-5-(2-naphthylthio)thieno[2,3-d]pyrimidin-4(3H)-one
-
-
2-amino-6-ethyl-5-(phenylsulfanyl)thieno[2,3-d]pyrimidin-4(3H)-one
-
-
2-amino-6-ethyl-5-(pyridin-4-ylsulfanyl)thieno[2,3-d]pyrimidin-4(3H)-one
-
-
2-amino-6-ethyl-5-[(4-fluorophenyl)sulfanyl]thieno[2,3-d]pyrimidin-4(3H)-one
-
-
2-amino-6-ethyl-5-[(4-nitrophenyl)sulfanyl]thieno[2,3-d]pyrimidin-4(3H)-one
-
-
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
4-amino-N10-methylfolic acid
-
-
5'-CGCGGTACGGACACCGCGCG-3'
-
targets the TS mRNA translation start site TSS and increases the thymidylate synthase gene transcription in HeLa cell
-
5,10-methenyltetrahydrofolylhexa-gamma-L-glutamate
-
-
5-fluoro-2'-deoxyuridine-5'-monophosphate
-
-
5-fluoro-2'-deoxyuridylic acid
-
-
5-fluorodeoxyuridine
5-fluoropyrimidine-2,4(1H,3H)-dione
-
-
5-fluorouracil
5-fluorouridine
-
-
5-Formyl-2'-deoxyuridylic acid
-
-
5-hydroseleno-2'-deoxyuridylic acid
-
-
5-hydroxy-methyl-2'-deoxyuridine 5'-monophosphate
-
-
5-Mercapto-2'-deoxyuridylic acid
-
-
5-trifluoromethyl-2'-deoxyuridylic acid
-
-
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
bromodeoxyuridine
-
-
capecitabine
-
prodrug of 5-fluorouracil
cytosine arabinoside
-
-
dihydropteroylpentaglutamate
-
-
ethyl methanesulfonate
-
-
fluoroorotic acid
-
-
gefitinib
GW1843U89
-
-
Iododeoxyuridine
-
-
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
methopterin
-
-
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-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-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]benzoyl)glutamic acid
-
-
N-([5-[2-(2,4-diaminoquinazolin-6-yl)ethyl]-2,3-dihydrothiophen-2-yl]carbonyl)-4-methylideneglutamic acid
-
-
N-[4-[(2,4-diamino-5-methyl-furo[2,3-d]pyrimidin-6-yl)thio]-benzoyl]-L-glutamic 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
-
dual inhibitor of thymidylate synthase and dihydrofolate reductase. Comparison with inhibitory effect on Escherichia coli and Toxoplasma gondii enzyme
N-[4-[(2-amino-6-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-5-yl)sulfanyl]benzoyl]-L-glutamic acid
-
potent inhibitor of thymidylate synthase
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
-
-
nolatrexed
-
transfection with p53 induces resistance to nolatrexed
OSI-7904L
pemetrexed
piritrexim
-
-
plevitrexed
-
-
propylene diphosphonate
-
mixed competitive-noncompetitive inhibitor with respect to dUMP
pteroyldiglutamate
-
-
Pteroylheptaglutamate
-
-
pteroylhexaglutamate
-
-
pteroylmonoglutamate
-
-
pteroylpentaglutamate
-
-
pteroylpolyglutamate
-
-
pteroyltetraglutamate
-
-
Pteroyltriglutamate
-
-
raltitrexed
Thymitaq
-
-
TomudexR
-
-
trimethoprim
-
-
trimetrexate
-
-
ZD1694
-
-
additional information
-
5FU-LV, combination of 5-fluorouracil and leucovorin
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2,3-Dimercaptopropanol
-
absolute requirement for a thiol, synthetase shows greatly dimished activity in absence
dithiothreitol
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0007 - 0.0026
2'-deoxyuridylate
0.0029 - 0.045
5,10-methylenetetrahydrofolate
0.00085 - 0.179
dUMP
0.0018 - 0.0037
2'-deoxyuridylate
0.0015 - 0.0524
5,10-methylenetetrahydrofolate
0.031
5,10-methylenetetrahydropteroylglutamate
-
-
0.0022
5,10-methylenetetrahydropteroylpentaglutamate
-
-
0.0023 - 0.134
dUMP
0.008 - 0.031
methylenetetrahydrofolate
0.0065
[6R]methylenetetrahydropteroyldiglutamate
-
-
0.0043
[6R]methylenetetrahydropteroylglutamate
-
-
0.0043
[6R]methylenetetrahydropteroylheptaglutamate
-
-
0.0087
[6R]methylenetetrahydropteroylhexaglutamate
-
-
0.0083
[6R]methylenetetrahydropteroylpentaglutamate
-
-
0.0109
[6R]methylenetetrahydropteroyltetraglutamate
-
-
0.0035
[6R]methylenetetrahydropteroyltriglutamate
-
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.52 - 0.54
5,10-methylenetetrahydrofolate
0.03 - 3.11
dUMP
3.9 - 48
5,10-methylenetetrahydrofolate
3.9 - 48
dUMP
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
120 - 220
5,10-methylenetetrahydrofolate
0.00000016 - 180
dUMP
70 - 3200
5,10-methylenetetrahydrofolate
720 - 6150
dUMP
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0027
1,3-propanediphosphonic acid
pH 7.2, 22°C
0.000038
ZD9331
pH 7.2, 22°C
0.0016
10-formyldihydropteroylpentaglutamate
-
-
0.0011 - 0.0054
5-fluoro-2'-deoxyuridine-5'-monophosphate
0.0000017
5-fluoro-2'-deoxyuridylic acid
-
-
0.00001
5-Formyl-2'-deoxyuridylic acid
-
-
0.00001 - 0.00004
5-Mercapto-2'-deoxyuridylic acid
0.00001
5-trifluoromethyl-2'-deoxyuridylic acid
-
-
0.023
methotrexate
-
uncompetitive with methylene tetrahydrofolate
0.0000059 - 0.0000113
propylene diphosphonate
0.0132
pteroyldiglutamate
-
-
0.0034
Pteroylheptaglutamate
-
-
0.002
pteroylhexaglutamate
-
-
0.0076
pteroylmonoglutamate
-
-
0.001
pteroylpentaglutamate
-
-
0.0006
pteroyltetraglutamate
-
-
0.0034
Pteroyltriglutamate
-
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0000046
1-(5-cyano-1,6-dihydro-6-oxo-4-p-tolylpyrimidin-2-yl)-4-phenylthiosemicarbazide
Homo sapiens
pH 7.4, 30°C
0.000085
10-propargyl-5,8-dideazafolate
Homo sapiens
-
0.00197
2,4-dioxo-N-(2-(1-(m-tolyl)-1H-1,2,3-triazol-4-yl)phenyl)-1, 2, 3, 4-tetrahydropyrimidine-5-sulfonamide
Homo sapiens
pH 7.4, 30°C
0.000013
2-(2-(4-hydroxybenzylidene)hydrazinyl)-6-oxo-4-(p-tolyl)-1,6-dihydropyrimidine-5-carbonitrile
Homo sapiens
pH 7.4, 30°C
0.00011
2-amino-5-[(3,4-dichlorophenyl)sulfanyl]-6-methylthieno[2,3-d]pyrimidin-4(3H)-one
Homo sapiens
-
0.00012
2-amino-6-methyl-5-(2-naphthylsulfanyl)thieno[2,3-d]pyrimidin-4(3H)-one
Homo sapiens
-
0.00011
2-amino-6-methyl-5-[(4-nitrophenyl)sulfanyl]thieno[2,3-d]pyrimidin-4(3H)-one
Homo sapiens
-
0.0000081
2-chloro-N'-[5-methyl-4-(4-methylphenyl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetohydrazide
Homo sapiens
pH 7.4, 30°C
0.0000044
2-hydrazinyl-1,6-dihydro-6-oxo-4-p-tolyl pyrimidine-5-carbonitrile
Homo sapiens
pH 7.4, 30°C
0.0000047
4-chloro-N'-(5-cyano-1,6-dihydro-6-oxo-4-p-tolylpyrimidin-2-yl)benzohydrazide
Homo sapiens
pH 7.4, 30°C
0.063 - 0.3
CQLYQRSG
0.075 - 0.188
LCQFYVVN
0.057 - 0.5
LSCQLYQR
0.0000037
N',N'-diacetyl-N-(5-cyano-1,6-dihydro-6-oxo-4-p-tolylpyrimidin-2-yl)acetohydrazide
Homo sapiens
pH 7.4, 30°C
0.0000042
N'-(5-cyano-1,6-dihydro-6-oxo-4-p-tolylpyrimidin-2-yl)-4-nitrobenzohydrazide
Homo sapiens
pH 7.4, 30°C
0.0000157
N'-(5-cyano-1,6-dihydro-6-oxo-4-p-tolylpyrimidin-2-yl)benzohydrazide
Homo sapiens
pH 7.4, 30°C
0.00087
N-(2-(1-(2-chlorophenyl)-1H-1,2,3-triazol-4-yl) phenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-sulfonamide
Homo sapiens
pH 7.4, 30°C
0.0006
N-(2-(1-(3-chlorophenyl)-1H-1,2,3-triazol-4-yl) phenyl)-2,4-dioxo-1, 2,3,4-tetrahydropyrimidine-5-sulfonamide
Homo sapiens
pH 7.4, 30°C
0.00013
N-(2-(1-(4-chlorophenyl)-1H-1,2,3-triazol-4-yl) phenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-sulfonamide
Homo sapiens
pH 7.4, 30°C
0.00128
N-(3-(1-(2-chlorophenyl)-1H-1,2,3-triazol-4-yl) phenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-sulfonamide
Homo sapiens
pH 7.4, 30°C
0.00056
N-(3-(1-(3-chlorophenyl)-1H-1,2,3-triazol-4-yl) phenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-sulfonamide
Homo sapiens
pH 7.4, 30°C
0.00045
N-(3-(1-(4-chlorophenyl)-1H-1,2,3-triazol-4-yl) phenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-sulfonamide
Homo sapiens
pH 7.4, 30°C
0.00004
N-(4-((2-amino-6-methyl-4-oxo-3,4-dihydrothieno(2,3-d)pyrimidin-5-yl)sulfanyl)benzoyl)-L-glutamic acid
Homo sapiens
potent inhibitor of human TS and of human DHFR, it is a novel dual TS-DHFR inhibitor, 330-fold more potent than pemetrexed
0.000054
N-(4-((2-amino-6-methyl-4-oxo-4,7-dihydro-3H-pyrrolo(2,3-d)pyrimidin-5-yl)thio)benzoyl)-L-glutamic acid
Homo sapiens
potent inhibitor of human TS and moderate inhibitor of human DHFR
0.00165
N-(4-(1-(2-chlorophenyl)-1H-1,2,3-triazol-4-yl) phenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-sulfonamide
Homo sapiens
pH 7.4, 30°C
0.00158
N-(4-(1-(3-chlorophenyl)-1H-1,2,3-triazol-4-yl) phenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-sulfonamide
Homo sapiens
pH 7.4, 30°C
0.00074
N-(4-(1-(4-chlorophenyl)-1H-1,2,3-triazol-4-yl) phenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-sulfonamide
Homo sapiens
pH 7.4, 30°C
0.00004
N-[4-[(2-amino-6-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-5-yl)sulfanyl]benzoyl]-L-glutamic acid
Homo sapiens
-
0.0095
pemetrexed
Homo sapiens
-
0.056 - 0.3
QFYVVNSE
0.03 - 0.3
SELSCQLY
0.05 - 0.3
VNSELSCQ
0.057 - 0.3
YVVNSELS
0.000054
(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
Homo sapiens
-
-
0.000085
10-propargyl-5,8-dideazafolate
Homo sapiens
-
-
0.0046
2-amino-5-[(2,5-dimethoxyphenyl)sulfanyl]-6-ethylthieno[2,3-d]pyrimidin-4(3H)-one
Homo sapiens
-
-
0.0011
2-amino-5-[(2-chlorophenyl)sulfanyl]-6-ethylthieno[2,3-d]pyrimidin-4(3H)-one
Homo sapiens
-
-
0.00023
2-amino-5-[(3,4-dichlorophenyl)thio]-6-ethylthieno[2,3-d]pyrimidin-4(3H)-one
Homo sapiens
-
-
0.00069
2-amino-5-[(3,5-dichlorophenyl)sulfanyl]-6-ethylthieno[2,3-d]-pyrimidin-4(3H)-one
Homo sapiens
-
-
0.0012
2-amino-5-[(3,5-dimethoxyphenyl)sulfanyl]-6-ethylthieno[2,3-d]pyrimidin-4(3H)-one
Homo sapiens
-
-
0.00038
2-amino-5-[(3-chlorophenyl)sulfanyl]-6-ethylthieno[2,3-d]pyrimidin-4(3H)-one
Homo sapiens
-
-
0.00039
2-amino-5-[(4-bromophenyl)sulfanyl]-6-ethylthieno[2,3-d]pyrimidin-4(3H)-one
Homo sapiens
-
-
0.00075
2-amino-5-[(4-chlorophenyl)sulfanyl]-6-ethylthieno[2,3-d]pyrimidin-4(3H)-one
Homo sapiens
-
-
0.0023
2-amino-6-ethyl-5-(2-naphthylthio)thieno[2,3-d]pyrimidin-4(3H)-one
Homo sapiens
-
-
0.0056
2-amino-6-ethyl-5-(phenylsulfanyl)thieno[2,3-d]pyrimidin-4(3H)-one
Homo sapiens
-
-
0.00028
2-amino-6-ethyl-5-(pyridin-4-ylsulfanyl)thieno[2,3-d]pyrimidin-4(3H)-one
Homo sapiens
-
-
0.0013
2-amino-6-ethyl-5-[(4-fluorophenyl)sulfanyl]thieno[2,3-d]pyrimidin-4(3H)-one
Homo sapiens
-
-
0.00022
2-amino-6-ethyl-5-[(4-nitrophenyl)sulfanyl]thieno[2,3-d]pyrimidin-4(3H)-one
Homo sapiens
-
-
0.029
methotrexate
Homo sapiens
-
at 30°C and pH 7.4
0.000046
N-(4-((2-amino-6-methyl-4-oxo-3,4-dihydro-5H-pyrrolo(3,2-d)pyrimidin-5-yl)methyl)benzoyl)-L-glutamic acid
Homo sapiens
-
potent dual inhibitor of human TS and human DHFR, 2-fold more potent than PDDF and 206-fold more potent than pemetrexed
0.000054
N-(4-((2-amino-6-methyl-4-oxo-4,7-dihydro-3H-pyrrolo(2,3-d)pyrimidin-5-yl)thio)benzoyl)-L-glutamic acid
Homo sapiens
-
potent inhibitor of human TS and moderate inhibitor of human DHFR
0.047
N-(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]benzoyl)glutamic acid
Homo sapiens
-
-
0.0049
N-([5-[2-(2,4-diaminoquinazolin-6-yl)ethyl]-2,3-dihydrothiophen-2-yl]carbonyl)-4-methylideneglutamic acid
Homo sapiens
-
-
0.0054
N-[4-[(2,4-diamino-5-methyl-furo[2,3-d]pyrimidin-6-yl)thio]-benzoyl]-L-glutamic acid
Homo sapiens
-
at 30°C and pH 7.4
0.000054
N-[4-[(2-amino-6-ethyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-5-yl)thio]benzoyl]-L-glutamic acid
Homo sapiens
-
-
0.000046
N-[4-[(2-amino-6-methyl-4-oxo-3,4-dihydro-5H-pyrrolo[3,2-d]pyrimidin-5-yl)methyl]benzoyl]-L-glutamic acid
Homo sapiens
-
-
0.00004
N-[4-[(2-amino-6-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-5-yl)sulfanyl]benzoyl]-L-glutamic acid
Homo sapiens
-
-
0.0048
N-[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]-2-fluorobenzoyl]-4-methylideneglutamic acid
Homo sapiens
-
-
0.008
N-[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid
Homo sapiens
-
-
0.0095
pemetrexed
0.00038
raltitrexed
Homo sapiens
-
at 30°C and pH 7.4
0.00144 - 0.034
ZD1694
additional information
N-[4-[2-(2,4-diamino-7H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-4-methylideneglutamic acid
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
1.26
pH 7.2, 22°C
0.0063
-
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7 - 8.1
-
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
adenocarcinoma
Manually annotated by BRENDA team
-
normal human fibroblast cell line immortalized by SV40
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
-
additionally transfected with pLGC-hUgi and pLGCX plasmids
Manually annotated by BRENDA team
-
highest thymidylate synthase expression
Manually annotated by BRENDA team
-
colorectal cancer cell, mutated subline of Lovo-92 cell
Manually annotated by BRENDA team
-
colorectal cancer cell harboring a functionally inactive p53
Manually annotated by BRENDA team
-
human NSCLC cell line
Manually annotated by BRENDA team
-
human NSCLC cell line
Manually annotated by BRENDA team
-
human NSCLC cell line
Manually annotated by BRENDA team
-
human NSCLC cell line
Manually annotated by BRENDA team
-
human NSCLC cell line
Manually annotated by BRENDA team
-
human NSCLC cell line
Manually annotated by BRENDA team
-
epithelial ovarian cancer cell line resistant to cisplatin
Manually annotated by BRENDA team
-
derived from primary malignant melanoma
Manually annotated by BRENDA team
additional information
-
NCI60 panel of 60 human tumor cell lines, the NCI-60 model is able to provide interesting information about the role of TYMS gene polymorphisms on TYMS mRNA expression and catalytic activity
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
physiological function
-
the enzyme is essential for the de novo synthesis of DNA
additional information
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
TYSY_HUMAN
313
0
35716
Swiss-Prot
other Location (Reliability: 3)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
148000
presence of inhibitor 1,3-propanediphosphonic acid, dynamic light scattering
75000
dynamic light scattering
33000
-
2 * 33000, SDS-PAGE
35000
-
2 * 35000, SDS-PAGE
66000
-
gel filtration
76000
-
-
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer
dimer
homodimer
-
x-ray crystallography
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
apo-enzyme crystallized in the active form with sulfate ions
grown in low-salt conditions, 100 mM Tris, pH 9.0, 20 mM beta-mercaptoethanol, 3 mM KH2PO4, and 10-20% PEG 4K, by hanging drop diffusion at 4 °C
hanging drop vapor diffusion method, using 2.0 M ammonium sulfate, 0.1 M Tris, pH 8.5, and 20 mM beta-mercaptoethanol
in complex with inhibitor 1,3-propanediphosphonic acid, to 2.5 A resolution
in-silico docking analysis of phytoconstituents from Crocus sativus, Curcuma longa, Cassia occidentalis and Moringa oleifera
ligand-free, binary and ternary complex structures with phosphate ions and dUMP
molecular docking of inhibitors
molecular modeling of complex with inhibitor N-[4-[(2-amino-6-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-5-yl)sulfanyl]benzoyl]-L-glutamic acid. The 6-methyl moiety of of the inhibitor makes important hydrophobic contacts with Trp109 and also serves to lock the 5-position side chain into favorable, low-energy conformations for thymidlyate synthase binding
mutant K47A in complex with inhibitor CQLYQRSG
wild-type and mutant R163K. Data show that all subunits of the mutant are in the active conformation, while wild-type crystallizes as the inactive conformer. Structure reveals differences in the environment of catalytic residue Cys195
crystals grown by vapor diffusion method in hanging drop setup
-
hanging-drop vapour diffusion method
mutant P254S
-
V3L, V3F and V3Y mutant enzymes, hanging drop vapor diffusion method, using 100 mM Tris-base, pH 8.5, 20 mM 2-mercaptoethanol, 32-40% (w/v) ammonium sulfate and 16-24% (w/v) polyethylene glycol 4000
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
A191K
F59A
crucial dimer interface residue
K47A
mutation at dimer interface
L198A
crucial dimer interface residue
L198P
the mutant enzyme displays a kcat value of 2fold lower than wild type
M190E
the mutant enzyme displays a kcat value of 5.9fold lower than wild type
M190K
R163K
Y202A
crucial dimer interface residue, activity similar to wild-type
A17T/D116A/D254E
-
the mutant shows decreased sensitivity towards 5-fluorodeoxyuridine compared to the wild type enzyme
A191K
-
the mutant exhibits about 25% of the catalytic activity of the wild type enzyme. The mutant exhibits nonhyperbolic behavior with respect to dUMP and inhibition of catalysis is reversed by substrate saturation
D254N
-
the mutant shows increased sensitivity towards 5-fluorodeoxyuridine compared to the wild type enzyme
E30W
-
the mutant shows 100times lower specific activity with respect to the wild type enzyme and is resistant to 5-fluoro-2'-deoxyuridine-5'-monophosphate (6fold higher inhibition constant than the wild type enzyme)
G52S
-
the mutant shows increased sensitivity towards 5-fluorodeoxyuridine compared to the wild type enzyme
M190K
-
the mutant exhibits less than1% of the catalytic activity of the wild type enzyme
R163K
-
the mutant exhibits an increase in catalytic activity and shows significantly reduced phosphorylation compared to the wild type enzyme
T51S
-
the mutant shows increased sensitivity towards 5-fluorodeoxyuridine compared to the wild type enzyme
T51S/G52S
-
the mutant shows increased sensitivity towards 5-fluorodeoxyuridine compared to the wild type enzyme
T51S/K82Q/K99E/N171S
-
the mutant shows increased sensitivity towards 5-fluorodeoxyuridine compared to the wild type enzyme
T53S/Y258F
-
the mutant shows sensitivity towards 5-fluorodeoxyuridine similar to the wild type enzyme
V3A
-
the mutant enzyme has an intracellular half-life of approximately 6 h after treatment with cycloheximide
V3F
-
the mutant enzyme has an intracellular half-life of approximately 3.5 h after treatment with cycloheximide
V3L
-
the mutant enzyme has an intracellular half-life of approximately 2.5 h after treatment with cycloheximide
V3T
-
the mutant enzyme has an intracellular half-life of approximately 24 h after treatment with cycloheximide
V3Y
-
the mutant enzyme has an intracellular half-life of approximately 2.5 h after treatment with cycloheximide
Y258F
-
the mutant shows decreased sensitivity towards 5-fluorodeoxyuridine compared to the wild type enzyme
additional information
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
enzyme is stabilized by addition of 20-120 mM dithiothreitol + bovine serum albumin
-
stable to protein denaturants and limited proteolysis
-
the wild type enzyme has an intracellular half-life of approximately 6 h after treatment with cycloheximide
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-25°C enzyme retains activity for 3 months when stored in presence of thiols, without thiols enzyme loses all activity in 2 days
-
4°C enzyme retains activity for 3 months when stored in presence of thiols, without thiols enzyme loses all activity in 2 days
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
Blue-Sepharose column chromatography and Q-Sepharose column chromatography
recombinant enzyme
partially
-
Pro-254 mutant enzymes
-
recombinant enzyme
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
Escherichia coli NM522 cells used for cloning and library construction, Escherichia coli chi2913recA lacking TS used for expression by complementation
expressed in Escherichia coli strain TX61
expression in Escherichia coli
plasmid containing the mutation was transformed into the Escherichia coli TX61-(thyA-) bacterial strain that does not produce its own thymidylate synthase enzyme
bacterial expression vector for overproduction in Escherichia coli
-
cDNAs from Thymitaq resistant clones, gene amplification with plasmid pET-17xb, expressed in Escherichia coli BL21(DE3)
-
Escherichia coli NM522 cells used for cloning and library construction, Escherichia coli chi2913recA lacking TS used for expression by complementation
-
expressed in Escherichia coli BL21 strain DE3pLysS
-
expressed in Escherichia coli strain K562
-
expressed in Escherichia coli strain TX61
-
expressed in Escherichia coli strain TX61- cells and in the RJK88.13 cell line (an enzyme-deficient derivative of V79 Chinese hamster lung cells)
-
mutant P254D cDNA cloned into SacII/XhoI sites of the HaMSV retroviral vector and transfected into the TS negative cell line RJK88.13
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
decreased mRNA expression after treatment with sodium butyrate or suberoylanilide hydroxamic acid
-
there is an approximately 2fold inverse relationship between thymidylate synthase expression and response to 5-fluoruracil
-
thymidylate synthase antisense oligodeoxynucleotide (ODN) 491 decreases thymidylate protein levels in HeLa cells with a concomitant increase in sensitivity to thymidylate synthase-targeting chemotherapeutics. In MCF-7 cells, ODN491 treatment is less effective at reducing thymidylate synthase mRNA and does not reduce thymidylate synthase protein, nor does it enhance sensitivity to thymidylate synthase-targeting or other chemotherapeutics. Treatment with either ODN 83 or ODN 491 reduces 6-fluoro-dUMP binding in HeLa cells by 59% and 62%, respectively, compared with control
-
thymidylate synthase mRNA levels of large-cell lung carcinoma cells are comparable of those of squamous cell carcinoma cells, but significantly higher than those of adenocarcinoma cells
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
medicine
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Blakeley, R.L.
The biosythesis of thymidylic acid. IV. Further studies on thymidylate synthetase
J. Biol. Chem.
238
2113-2118
1963
Escherichia coli, Enterococcus faecalis, Homo sapiens
-
Manually annotated by BRENDA team
Fridland, A.; Langenbach, R.J.; Heidelberger, C.
Purification of thymidylate synthetase from Ehrlich ascites carcinoma cells
J. Biol. Chem.
246
7110-7114
1971
Bos taurus, Gallus gallus, Escherichia coli, Enterococcus faecalis, Homo sapiens, Lacticaseibacillus casei, Mus musculus
Manually annotated by BRENDA team
Loeble, R.B.; Dunlap, R.B.
Characterization of the subunits of thymidylate synthetase
Biochem. Biophys. Res. Commun.
49
1671-1677
1972
Homo sapiens, Lacticaseibacillus casei
Manually annotated by BRENDA team
Danenberg, P.V.
Thymidylate synthetase - a target enzyme in cancer chemotherapy
Biochim. Biophys. Acta
473
73-92
1977
Enterococcus faecalis, Escherichia coli, Escherichia coli B / ATCC 11303, Homo sapiens, Lacticaseibacillus casei, Mus musculus, Streptococcus pneumoniae
Manually annotated by BRENDA team
Dolnick, B.J.; Cheng, Y.C.
Human thymidylate synthetase. II. Derivatives of pteroylmono- and -polyglutamates as substrates and inhibitors
J. Biol. Chem.
253
3563-3567
1978
Escherichia coli, Escherichia coli B / ATCC 11303, Escherichia coli R2, Homo sapiens, Lacticaseibacillus casei
Manually annotated by BRENDA team
Lockshin, A.; Moran, R.G.; Danenberg, P.V.
Thymidylate synthetase purified to homogeneity from human leukemic cells
Proc. Natl. Acad. Sci. USA
76
750-754
1979
Escherichia phage T2, Bos taurus, Escherichia coli, Homo sapiens, Lacticaseibacillus casei
Manually annotated by BRENDA team
Rode, W.; Scanlon, K.J.; Hynes, J.; Bertino, J.R.
Purification of mammalian tumor (L1210) thymidylate synthetase by affinity chromatography on stable biospecific adsorbent. Stabilization of the enzyme with neutral detergents
J. Biol. Chem.
254
11538-11543
1979
Escherichia coli, Homo sapiens, Lacticaseibacillus casei, Mus musculus
Manually annotated by BRENDA team
Bisson, L.F.; Thorner, J.
Thymidylate synthetase from Saccharomyces cerevisiae. Purification and enzymic properties
J. Biol. Chem.
256
12456-12462
1981
Saccharomyces cerevisiae, Gallus gallus, Enterococcus faecalis, Homo sapiens, Lacticaseibacillus casei, Mus musculus
Manually annotated by BRENDA team
Banerjee, C.K.; Bennett, L.L.; Brockman, R.W.; Sani, B.P.; Temple, C.
A convenient procedure for purification of thymidylate synthase from L1210 cells
Anal. Biochem.
121
275-280
1982
Gallus gallus, Homo sapiens, Lacticaseibacillus casei, Mus musculus
Manually annotated by BRENDA team
Pattanakitsakul, S.N.; Ruenwongsa, P.
Characterization of thymidylate synthetase and dihydrofolate reductase from Plasmodium berghei
Int. J. Parasitol.
14
513-520
1984
Crithidia fasciculata, Streptococcus pneumoniae, Escherichia coli, Homo sapiens, Lacticaseibacillus casei, Leishmania major, Plasmodium berghei
Manually annotated by BRENDA team
Nakata, R.; Tsukamoto, I.; Miyoshi, M.; Kojo, S.
Purification and characterization of thymidylate synthetase from rat regenerating liver
Biochim. Biophys. Acta
924
297-302
1987
Homo sapiens, Lacticaseibacillus casei, Mus musculus, Rattus norvegicus, Rattus norvegicus Wistar, Saccharomyces cerevisiae
Manually annotated by BRENDA team
Radparvar, S.; Houghton, P.J.; Houghton, J.A.
Characteristics of thymidylate synthase purified from a human colon adenocarcinoma
Arch. Biochem. Biophys.
260
342-350
1988
Homo sapiens, Sus scrofa
Manually annotated by BRENDA team
Balinska, M.; Rhee, M.; Whiteley, J.M.; Priest, D.G.; Galivan, J.
Inhibition of mammalian thymidylate synthase by 10-formyltetrahydropteroylpolyglutamate
Arch. Biochem. Biophys.
284
219-222
1991
Homo sapiens, Mus musculus, Rattus norvegicus
Manually annotated by BRENDA team
Zhang, H.; Cisneros, R.J.; Deng, W.; Zapf, J.W.; Johnson, L.F.; Dunlap, R.B.
Purification and characterization of recombinant mouse thymidylate synthase
Biochim. Biophys. Acta
1077
35-46
1991
Homo sapiens, Lacticaseibacillus casei, Mus musculus
Manually annotated by BRENDA team
Livi, L.L.; Edman, U.; Schneider, G.P.; Greene, P.J.; Santi, D.V.
Cloning, expression and characterization of thymidylate synthase from Cryptococcus neoformans
Gene
150
221-226
1994
Tequatrovirus T4, Candida albicans, Homo sapiens, Lacticaseibacillus casei, Mus musculus, Pneumocystis carinii, Cryptococcus neoformans (P0CS13), Cryptococcus neoformans, Cryptococcus neoformans B-3501A (P0CS13)
Manually annotated by BRENDA team
So, N.N.C.; Wong, P.C.L.; Ko, R.C.
Angiostrongylus cantonensis: Characterization of thymidylate synthetase
Exp. Parasitol.
79
526-535
1994
Aedes aegypti, Angiostrongylus cantonensis, Bos taurus, Saccharomyces cerevisiae, Brugia pahangi, Candida albicans, Gallus gallus, Crithidia fasciculata, Homo sapiens, Leishmania major, Mus musculus, Plasmodium falciparum, Rattus norvegicus, Sus scrofa, Toxoplasma gondii
Manually annotated by BRENDA team
Schiffer, C.A.; Clifton, I.J.; Davisson, V.J.; Santi, D.V.; Stroud, R.M.
Crystal structure of human thymidylate synthase: a structural mechanism for guiding substrates into the active site
Biochemistry
34
16279-16287
1995
Homo sapiens
Manually annotated by BRENDA team
Voeller, D.M.; Changchien, L.M.; Maley, G.F.; Maley, F.; Takechi, T.; Turner, R.E.; Montfort, W.R.; Allegra, C.J.; Chu, E.
Characterization of a specific interaction between Escherichia coli thymidylate synthase and Escherichia coli thymidylate synthase mRNA
Nucleic Acids Res.
23
869-875
1995
Tequatrovirus T4, Escherichia coli, Enterococcus faecium, Homo sapiens
Manually annotated by BRENDA team
Hekmat-Nejad, M.; Rathod, P.K.
Kinetics of Plasmodium flaciparum thymidylate synthase: interactions with high-affinity metabolites of 5-fluoroorotate and D1694
Antimicrob. Agents Chemother.
40
1628-1632
1996
Crithidia fasciculata, Escherichia coli, Homo sapiens, Leishmania major, Mus musculus, Plasmodium berghei, Plasmodium falciparum, Plasmodium yoelii
Manually annotated by BRENDA team
Spencer, H.T.; Villafranca, J.E.; Appleman, J.R.
Kinetic scheme for thymidylate synthase from Escherichia coli: determination from measurements of ligand binding, primary and secondary isotope effects, and pre-steady-state catalysis
Biochemistry
36
4212-4222
1997
Tequatrovirus T4, Candida albicans, Escherichia coli, Homo sapiens, Lacticaseibacillus casei, Mus musculus
Manually annotated by BRENDA team
Tong, Y.; Liu-Chen, X.; Ercikan-Abali, E.A.; Capiaux, G.M.; Zhao, S.C.; Banerjee, D.; Bertino, J.R.
Isolation and characterization of Thymitaq (AG337) and 5-fluoro-2-deoxyuridylate-resistant mutants of human thymidylate synthase from ethyl methanesulfonate-exposed human sarcoma HT1080 cells
J. Biol. Chem.
273
11611-11618
1998
Escherichia coli, Homo sapiens, Lacticaseibacillus casei, Cryptococcus neoformans (P0CS13), Cryptococcus neoformans B-3501A (P0CS13)
Manually annotated by BRENDA team
Mahdavian, E.; Spencer, H.T.; Dunlap, R.B.
Kinetic studies on drug-resistant variants of Escherichia coli thymidylate sythase: Functional effects of amino acid sunstitutions at residue 4
Arch. Biochem. Biophys.
368
257-264
1999
Escherichia coli, Homo sapiens
Manually annotated by BRENDA team
Steadman, D.J.; Spencer, H.T.; Dunlap, R.B.; Berger, S.H.
Substitution at residue 214 of human thymidylate synthase alters nucleotide binding and isomerization of ligand-protein complexes
Biochemistry
38
5582-5587
1999
Escherichia coli, Homo sapiens, Lacticaseibacillus casei
Manually annotated by BRENDA team
Fantz, C.; Shaw, D.; Jennings, W.; Forsthoefel, A.; Kitchens, M.; Phan, J.; Minor, W.; Lebioda, L.; Berger, F.G.; Spencer, H.T.
Drug-resistant variants of Escherichia coli thymidylate synthase: effects of substitutions at Pro-254
Mol. Pharmacol.
57
359-366
2000
Homo sapiens, Mus musculus, Escherichia coli (P0A884), Escherichia coli
Manually annotated by BRENDA team
Jarmula, A.; Les, A.; Rode, W.
Different activities of 5-hydroxy-dUMP and 5-hydroxymethyl-dUMP in thymidylate synthase-catalyzed reaction in view of molecular modeling and structural studies
Bioorg. Chem.
28
156-162
2000
Homo sapiens
Manually annotated by BRENDA team
Phan, J.; Mahdavian, E.; Nivens, M.C.; Minor, W.; Berger, S.; Spencer, H.T.; Dunlap, R.B.; Lebioda, L.
Catalytic cysteine of thymidylate synthase is activated upon substrate binding
Biochemistry
39
6969-6978
2000
Homo sapiens, Lacticaseibacillus casei, Escherichia coli (P0A884), Escherichia coli
Manually annotated by BRENDA team
Golos, B.; Dzik, J.M.; Kazimierczuk, Z.; Ciesla, J.; Zielinski, Z.; Jankowska, J.; Kraszewski, A.; Stawinski, J.; Rode, W.; Shugar, D.
Interaction of thymidylate synthase with the 5'-thiophosphates, 5'-dithiophosphates, 5'-H-phosphonates and 5'-S-thiosulfates of 2'-deoxyuridine, thymidine and 5-fluoro-2'-deoxyuridine
Biol. Chem.
382
1439-1445
2001
Escherichia coli, Homo sapiens, Lacticaseibacillus casei, Mus musculus, Pneumocystis carinii, Rattus norvegicus, Trichinella pseudospiralis, Trichinella spiralis
Manually annotated by BRENDA team
Kawate, H.; Landis, D.M.; Loeb, L.A.
Distribution of mutations in human thymidylate synthase yielding resistance to 5-fluorodeoxyuridine
J. Biol. Chem.
277
36304-36311
2002
Homo sapiens (P04818), Homo sapiens
Manually annotated by BRENDA team
Gangjee, A.; Li, W.; Yang, J.; Kisliuk, R.L.
Design, synthesis, and biological evaluation of classical and nonclassical 2-amino-4-oxo-5-substituted-6-methylpyrrolo[3,2-d]pyrimidines as dual thymidylate synthase and dihydrofolate reductase inhibitors
J. Med. Chem.
51
68-76
2008
Escherichia coli, Homo sapiens, Toxoplasma gondii
Manually annotated by BRENDA team
Lovelace, L.L.; Gibson, L.M.; Lebioda, L.
Cooperative inhibition of human thymidylate synthase by mixtures of active site binding and allosteric inhibitors
Biochemistry
46
2823-2830
2007
Homo sapiens, Homo sapiens (P04818)
Manually annotated by BRENDA team
Gibson, L.M.; Lovelace, L.L.; Lebioda, L.
The R163K mutant of human thymidylate synthase is stabilized in an active conformation: structural asymmetry and reactivity of cysteine 195
Biochemistry
47
4636-4643
2008
Homo sapiens (P04818), Homo sapiens
Manually annotated by BRENDA team
Giovannetti, E.; Backus, H.H.; Wouters, D.; Ferreira, C.G.; van Houten, V.M.; Brakenhoff, R.H.; Poupon, M.F.; Azzarello, A.; Pinedo, H.M.; Peters, G.J.
Changes in the status of p53 affect drug sensitivity to thymidylate synthase (TS) inhibitors by altering TS levels
Br. J. Cancer
96
769-775
2007
Homo sapiens
Manually annotated by BRENDA team
Clamp, A.R.; Schoeffski, P.; Valle, J.W.; Wilson, R.H.; Marreaud, S.; Govaerts, A.S.; Debois, M.; Lacombe, D.; Twelves, C.; Chick, J.; Jayson, G.C.; Jayson, G.C.
A phase I and pharmacokinetic study of OSI-7904L, a liposomal thymidylate synthase inhibitor in combination with oxaliplatin in patients with advanced colorectal cancer
Cancer Chemother. Pharmacol.
61
579-585
2008
Homo sapiens
Manually annotated by BRENDA team
Pillai, R.G.; Forster, M.; Perumal, M.; Mitchell, F.; Leyton, J.; Aibgirhio, F.I.; Golovko, O.; Jackman, A.L.; Aboagye, E.O.
Imaging pharmacodynamics of the alpha-folate receptor-targeted thymidylate synthase inhibitor BGC 945
Cancer Res.
68
3827-3834
2008
Homo sapiens
Manually annotated by BRENDA team
Luo, Y.; Walla, M.; Wyatt, M.D.
Uracil incorporation into genomic DNA does not predict toxicity caused by chemotherapeutic inhibition of thymidylate synthase
DNA Repair
7
162-169
2008
Homo sapiens
Manually annotated by BRENDA team
Waldman, B.C.; Wang, Y.; Kilaru, K.; Yang, Z.; Bhasin, A.; Wyatt, M.D.; Waldman, A.S.
Induction of intrachromosomal homologous recombination in human cells by raltitrexed, an inhibitor of thymidylate synthase
DNA Repair
7
1624-1635
2008
Homo sapiens
Manually annotated by BRENDA team
Nief, N.; Le Morvan, V.; Robert, J.
Involvement of gene polymorphisms of thymidylate synthase in gene expression, protein activity and anticancer drug cytotoxicity using the NCI-60 panel
Eur. J. Cancer
43
955-962
2007
Homo sapiens
Manually annotated by BRENDA team
Jason, T.L.; Berg, R.W.; Vincent, M.D.; Koropatnick, J.
Antisense targeting of thymidylate synthase (TS) mRNA increases TS gene transcription and TS protein: effects on human tumor cell sensitivity to TS enzyme-inhibiting drugs
Gene Expr.
13
227-239
2007
Homo sapiens
Manually annotated by BRENDA team
Curtin, K.; Ulrich, C.M.; Samowitz, W.S.; Bigler, J.; Caan, B.; Potter, J.D.; Slattery, M.L.
Thymidylate synthase polymorphisms and colon cancer: associations with tumor stage, tumor characteristics and survival
Int. J. Cancer
120
2226-2232
2007
Homo sapiens
Manually annotated by BRENDA team
Gangjee, A.; Qiu, Y.; Li, W.; Kisliuk, R.L.
Potent dual thymidylate synthase and dihydrofolate reductase inhibitors: classical and nonclassical 2-amino-4-oxo-5-arylthio-substituted-6-methylthieno[2,3-d]pyrimidine antifolates
J. Med. Chem.
51
5789-5797
2008
Escherichia coli, Toxoplasma gondii, Homo sapiens (P04818), Homo sapiens
Manually annotated by BRENDA team
Okabe, T.; Okamoto, I.; Tsukioka, S.; Uchida, J.; Iwasa, T.; Yoshida, T.; Hatashita, E.; Yamada, Y.; Satoh, T.; Tamura, K.; Fukuoka, M.; Nakagawa, K.
Synergistic antitumor effect of S-1 and the epidermal growth factor receptor inhibitor gefitinib in non-small cell lung cancer cell lines: role of gefitinib-induced down-regulation of thymidylate synthase
Mol. Cancer Ther.
7
599-606
2008
Homo sapiens
Manually annotated by BRENDA team
Codacci-Pisanelli, G.; Noordhuis, P.; van der Wilt, C.L.; Peters, G.J.
Selective protection by uridine of growth inhibition by 5-fluorouracil (5FU) mediated by 5FU incorporation into RNA, but not the thymidylate synthase mediated growth inhibition by 5FU-leucovorin
Nucleosides Nucleotides Nucleic Acids
27
733-739
2008
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Giovannetti, E.; Backus, H.H.; Wouters, D.; Peters, G.J.
Functional inactivity and mutations of p53 differentially affect sensitivity to 5-fluorouracil and antifolate inhibitors of thymidylate synthase (TS) by altering TS levels in colorectal cancer cells
Nucleosides Nucleotides Nucleic Acids
27
740-745
2008
Homo sapiens
Manually annotated by BRENDA team
Yan, S.; Niu, R.; Wang, Z.; Lin, X.
In vitro selected peptides bind with thymidylate synthase mRNA and inhibit its translation
Sci. China C Life Sci.
50
630-636
2007
Homo sapiens
Manually annotated by BRENDA team
Giudice, S.; Benassi, L.; Bertazzoni, G.; Costi, M.P.; Gelain, A.; Venturelli, A.; Bernardi, C.; Gualdi, G.; Coppi, A.; Rossi, T.; Giannetti, A.; Magnoni, C.
New thymidylate synthase inhibitors induce apoptosis in melanoma cell lines
Toxicol. in Vitro
21
240-248
2007
Homo sapiens
Manually annotated by BRENDA team
McGuire, J.J.; Haile, W.H.
Metabolism-blocked antifolates as potential anti-rheumatoid arthritis agents: 4-amino-4-deoxy-5,8,10-trideazapteroyl-D,L-4-methyleneglutamic acid (CH-1504) and its analogs
Biochem. Pharmacol.
77
1161-1172
2009
Homo sapiens
Manually annotated by BRENDA team
Showalter, S.L.; Showalter, T.N.; Witkiewicz, A.; Havens, R.; Kennedy, E.P.; Hucl, T.; Kern, S.E.; Yeo, C.J.; Brody, J.R.
Evaluating the drug-target relationship between thymidylate synthase expression and tumor response to 5-fluorouracil. Is it time to move forward?
Cancer Biol. Ther.
7
986-994
2008
Homo sapiens
Manually annotated by BRENDA team
Monica, V.; Scagliotti, G.V.; Ceppi, P.; Righi, L.; Cambieri, A.; Lo Iacono, M.; Saviozzi, S.; Volante, M.; Novello, S.; Papotti, M.
Differential thymidylate synthase expression in different variants of large-cell carcinoma of the lung
Clin. Cancer Res.
15
7547-7552
2009
Homo sapiens
Manually annotated by BRENDA team
Jason, T.L.; Figueredo, R.; Ferguson, P.J.; Vincent, M.D.; Berg, R.W.; Koropatnick, J.
ODN 491, a novel antisense oligodeoxynucleotide that targets thymidylate synthase, exerts cell-specific effects in human tumor cell lines
DNA Cell Biol.
27
229-240
2008
Homo sapiens
Manually annotated by BRENDA team
Bielas, J.H.; Schmitt, M.W.; Icreverzi, A.; Ericson, N.G.; Loeb, L.A.
Molecularly evolved thymidylate synthase inhibits 5-fluorodeoxyuridine toxicity in human hematopoietic cells
Hum. Gene Ther.
20
1703-1707
2009
Homo sapiens
Manually annotated by BRENDA team
Gangjee, A.; Li, W.; Kisliuk, R.L.; Cody, V.; Pace, J.; Piraino, J.; Makin, J.
Design, synthesis, and X-ray crystal structure of classical and nonclassical 2-amino-4-oxo-5-substituted-6-ethylthieno[2,3-d]pyrimidines as dual thymidylate synthase and dihydrofolate reductase inhibitors and as potential antitumor agents
J. Med. Chem.
52
4892-4902
2009
Escherichia coli, Homo sapiens, Toxoplasma gondii
Manually annotated by BRENDA team
Leclerc, G.J.; Mou, C.; Leclerc, G.M.; Mian, A.M.; Barredo, J.C.
Histone deacetylase inhibitors induce FPGS mRNA expression and intracellular accumulation of long-chain methotrexate polyglutamates in childhood acute lymphoblastic leukemia: implications for combination therapy
Leukemia
24
552-562
2010
Homo sapiens
Manually annotated by BRENDA team
Lovelace, L.L.; Johnson, S.R.; Gibson, L.M.; Bell, B.J.; Berger, S.H.; Lebioda, L.
Variants of human thymidylate synthase with loop 181-197 stabilized in the inactive conformation
Protein Sci.
18
1628-1636
2009
Homo sapiens (P04818), Homo sapiens
Manually annotated by BRENDA team
Gangjee, A.; Jain, H.D.; Phan, J.; Guo, X.; Queener, S.F.; Kisliuk, R.L.
2,4-Diamino-5-methyl-6-substituted arylthio-furo[2,3-d]pyrimidines as novel classical and nonclassical antifolates as potential dual thymidylate synthase and dihydrofolate reductase inhibitors
Bioorg. Med. Chem.
18
953-961
2010
Escherichia coli, Homo sapiens, Toxoplasma gondii
Manually annotated by BRENDA team
Huang, X.; Gibson, L.M.; Bell, B.J.; Lovelace, L.L.; Pena, M.M.; Berger, F.G.; Berger, S.H.; Lebioda, L.
Replacement of Val3 in human thymidylate synthase affects its kinetic properties and intracellular stability
Biochemistry
49
2475-2482
2010
Homo sapiens
Manually annotated by BRENDA team
Jarmula, A.; Fraczyk, T.; Cieplak, P.; Rode, W.
Mechanism of influence of phosphorylation on serine 124 on a decrease of catalytic activity of human thymidylate synthase
Bioorg. Med. Chem.
18
3361-3370
2010
Homo sapiens
Manually annotated by BRENDA team
Wang, Z.; Kohen, A.
Thymidylate synthase catalyzed H-transfers: two chapters in one tale
J. Am. Chem. Soc.
132
9820-9825
2010
Homo sapiens
Manually annotated by BRENDA team
Cardinale, D.; Salo-Ahen, O.; Guaitoli, G.; Ferrari, S.; Venturelli, A.; Franchini, S.; Battini, R.; Ponterini, G.; Wade, R.; Costi, M.
Design and characterization of a mutation outside the active site of human thymidylate synthase that affects ligand binding
Protein Eng.
23
81-89
2010
Homo sapiens
Manually annotated by BRENDA team
Luo, B.; Repalli, J.; Yousef, A.M.; Johnson, S.R.; Lebioda, L.; Berger, S.H.
Human thymidylate synthase with loop 181-197 stabilized in an inactive conformation: ligand interactions, phosphorylation, and inhibition profiles
Protein Sci.
20
87-94
2011
Homo sapiens
Manually annotated by BRENDA team
Cannazza, G.; Cazzato, A.S.; Marraccini, C.; Pavesi, G.; Pirondi, S.; Guerrini, R.; Pela, M.; Frassineti, C.; Ferrari, S.; Marverti, G.; Ponterini, G.; Costi, M.P.
Internalization and stability of a thymidylate synthase peptide inhibitor in ovarian cancer cells
J. Med. Chem.
57
10551-10556
2014
Homo sapiens
Manually annotated by BRENDA team
Wang, N.; McCammon, J.A.
Substrate channeling between the human dihydrofolate reductase and thymidylate synthase
Protein Sci.
25
79-86
2016
Homo sapiens (P04818), Homo sapiens
Manually annotated by BRENDA team
Deschamps, P.; Rety, S.; Bareille, J.; Leulliot, N.
Crystal structure of the active form of native human thymidylate synthase in the absence of bound substrates
Acta Crystallogr. Sect. F
73
336-341
2017
Homo sapiens (P04818), Homo sapiens
Manually annotated by BRENDA team
Amin, L.H.T.; Shawer, T.Z.; El-Naggar, A.M.; El-Sehrawi, H.M.A.
Design, synthesis, anticancer evaluation and docking studies of new pyrimidine derivatives as potent thymidylate synthase inhibitors
Bioorg. Chem.
91
103159
2019
Homo sapiens (P04818)
Manually annotated by BRENDA team
Li, X.Y.; Liang, J.W.; Mohamed O, K.; Zhang, T.J.; Lu, G.Q.; Meng, F.H.
Design, synthesis and biological evaluation of N-phenyl-(2,4-dihydroxypyrimidine-5-sulfonamido)benzoyl hydrazide derivatives as thymidylate synthase (TS) inhibitors and as potential antitumor drugs
Eur. J. Med. Chem.
154
267-279
2018
Homo sapiens (P04818)
Manually annotated by BRENDA team
Lu, G.Q.; Li, X.Y.; Mohamed O, K.; Wang, D.; Meng, F.H.
Design, synthesis and biological evaluation of novel uracil derivatives bearing 1, 2, 3-triazole moiety as thymidylate synthase (TS) inhibitors and as potential antitumor drugs
Eur. J. Med. Chem.
171
282-296
2019
Homo sapiens (P04818)
Manually annotated by BRENDA team
Heble, N.; Mavillapalli, R.; Selvaraj, R.; Jeyabalan, S.
Molecular docking studies of phytoconstituents identified in Crocus sativus, Curcuma longa, Cassia occidentalis and Moringa oleifera on thymidylate synthase - An enzyme target for anti-cancer activity
J. Appl. Pharm. Sci.
6
131-135
2016
Homo sapiens (P04818)
-
Manually annotated by BRENDA team
Chen, D.; Jansson, A.; Sim, D.; Larsson, A.; Nordlund, P.
Structural analyses of human thymidylate synthase reveal a site that may control conformational switching between active and inactive states
J. Biol. Chem.
292
13449-13458
2017
Homo sapiens (P04818), Homo sapiens
Manually annotated by BRENDA team
Antosiewicz, A.; Jarmula, A.; Przybylska, D.; Mosieniak, G.; Szczepanowska, J.; Kowalkowska, A.; Rode, W.; Ciesla, J.
Human dihydrofolate reductase and thymidylate synthase form a complex in vitro and co-localize in normal and cancer cells
J. Biomol. Struct. Dyn.
35
1474-1490
2017
Homo sapiens (P04818), Homo sapiens
Manually annotated by BRENDA team
Tochowicz, A.; Santucci, M.; Saxena, P.; Guaitoli, G.; Trande, M.; Finer-Moore, J.; Stroud, R.; Costi, M.
Alanine mutants of the interface residues of human thymidylate synthase decode key features of the binding mode of allosteric anticancer peptides
J. Med. Chem.
58
1012-1018
2015
Homo sapiens (P04818), Homo sapiens
Manually annotated by BRENDA team
Islam, Z.; Gurevic, I.; Strutzenberg, T.S.; Ghosh, A.K.; Iqbal, T.; Kohen, A.
Bacterial versus human thymidylate synthase Kinetics and functionality
PLoS ONE
13
e0196506
2018
Homo sapiens (P04818), Homo sapiens
Manually annotated by BRENDA team