Page last updated: 2024-10-24

thymidylate synthase activity

Definition

Target type: molecularfunction

Catalysis of the reaction: 5,10-methylenetetrahydrofolate + dUMP = 7,8-dihydrofolate + thymidylate. [EC:2.1.1.45, RHEA:12104]

Thymidylate synthase (TS) is a crucial enzyme involved in the synthesis of deoxythymidine monophosphate (dTMP), a key building block for DNA. Specifically, TS catalyzes the methylation of deoxyuridine monophosphate (dUMP) to dTMP using 5,10-methylenetetrahydrofolate as a one-carbon donor. This reaction is essential for DNA replication and repair, as dTMP is exclusively found in DNA and is not synthesized de novo from other nucleotides. The active site of TS exhibits a unique structural feature that allows it to bind both dUMP and methylenetetrahydrofolate. The enzyme undergoes significant conformational changes upon substrate binding, which is crucial for catalysis. This intricate mechanism ensures the precise and efficient conversion of dUMP to dTMP, thus maintaining the integrity of DNA synthesis.'
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Proteins (2)

ProteinDefinitionTaxonomy
Thymidylate synthaseA thymidylate synthase that is encoded in the genome of Escherichia coli K-12. [OMA:P0A884, PRO:DNx]Escherichia coli K-12
Thymidylate synthaseA thymidylate synthase that is encoded in the genome of human. [PRO:DNx, UniProtKB:P04818]Homo sapiens (human)

Compounds (25)

CompoundDefinitionClassesRoles
phenolphthaleinPhenolphthalein: An acid-base indicator which is colorless in acid solution, but turns pink to red as the solution becomes alkaline. It is used medicinally as a cathartic.phenols
trimethoprimtrimethoprim : An aminopyrimidine antibiotic whose structure consists of pyrimidine 2,4-diamine and 1,2,3-trimethoxybenzene moieties linked by a methylene bridge.

Trimethoprim: A pyrimidine inhibitor of dihydrofolate reductase, it is an antibacterial related to PYRIMETHAMINE. It is potentiated by SULFONAMIDES and the TRIMETHOPRIM, SULFAMETHOXAZOLE DRUG COMBINATION is the form most often used. It is sometimes used alone as an antimalarial. TRIMETHOPRIM RESISTANCE has been reported.
aminopyrimidine;
methoxybenzenes
antibacterial drug;
diuretic;
drug allergen;
EC 1.5.1.3 (dihydrofolate reductase) inhibitor;
environmental contaminant;
xenobiotic
1,8-naphthalenedicarboxylic acid anhydride1,8-naphthalenedicarboxylic acid anhydride: used as seed protector from herbicidescyclic dicarboxylic anhydride
fluorodeoxyuridylateFluorodeoxyuridylate: 5-Fluoro-2'-deoxyuridylate. An inhibitor of thymidylate synthetase. Formed from 5-fluorouracil or 5-fluorodeoxyuridine.pyrimidine 2'-deoxyribonucleoside 5'-monophosphate
2'-deoxyuridylic acid2'-deoxyuridylic acid: RN given refers to parent cpddeoxyuridine phosphate;
pyrimidine 2'-deoxyribonucleoside 5'-monophosphate
Escherichia coli metabolite;
metabolite;
mouse metabolite
dansyl hydrazine
methotrexatedicarboxylic acid;
monocarboxylic acid amide;
pteridines
abortifacient;
antimetabolite;
antineoplastic agent;
antirheumatic drug;
dermatologic drug;
DNA synthesis inhibitor;
EC 1.5.1.3 (dihydrofolate reductase) inhibitor;
immunosuppressive agent
n-(4-(n-((2,4-diaminofuro(2,3-d)pyrimidin-5-yl)methyl)amino)benzoyl)glutamic acidN-(4-(N-((2,4-diaminofuro(2,3-d)pyrimidin-5-yl)methyl)amino)benzoyl)glutamic acid: structure given in first source
n-4-hydroxy-2'-deoxycytidylic acidN-4-hydroxy-2'-deoxycytidylic acid: reversibly binds to thymidylate synthetase
flavin mononucleotideflavin mononucleotide;
vitamin B2
bacterial metabolite;
coenzyme;
cofactor;
human metabolite;
mouse metabolite
folic acidfolcysteine: used to promote fertility in chickens

vitamin B9 : Any B-vitamin that exhibits biological activity against vitamin B9 deficiency. Vitamin B9 refers to the many forms of folic acid and its derivatives, including tetrahydrofolic acid (the active form), methyltetrahydrofolate (the primary form found in blood), methenyltetrahydrofolate, folinic acid amongst others. They are present in abundance in green leafy vegetables, citrus fruits, and animal products. Lack of vitamin B9 leads to anemia, a condition in which the body cannot produce sufficient number of red blood cells. Symptoms of vitamin B9 deficiency include fatigue, muscle weakness, and pale skin.
folic acids;
N-acyl-amino acid
human metabolite;
mouse metabolite;
nutrient
raltitrexedN-acyl-amino acid
nolatrexednolatrexed: structure given in first source; RN given refers to dihydrochloride
ici 198583ICI 198583: RN & structure given in first source
n-(4(n-((2-amino-4-hydroxy-6-quinazolinyl)methyl)prop-2-ynylamino)benzoyl)-l-glutamic acid
1843u891843U89: structure given in first source; a folate analog
5,11-methenyltetrahydrohomofolate
pemetrexedpemetrexed disodium : An organic sodium salt that is the disodium salt of N-{4-[2-(2-amino-4-oxo-4,7-dihydro-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl}-L-glutamic acid. Inhibits thymidylate synthase (TS), 421 dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT).N-acyl-L-glutamic acid;
pyrrolopyrimidine
antimetabolite;
antineoplastic agent;
EC 1.5.1.3 (dihydrofolate reductase) inhibitor;
EC 2.1.1.45 (thymidylate synthase) inhibitor;
EC 2.1.2.2 (phosphoribosylglycinamide formyltransferase) inhibitor
n(10)-methylfolatefolic acids
cb 3717N-acyl-L-glutamic acid
cb 30865
ag 85AG 85: structure given in first source
cb 3705CB 3705: inhibitor of dihydrofolate reductase & thymidylate synthetase
2-desamino-2-methyl-5,8-dideazaisofolic acid2-desamino-2-methyl-5,8-dideazaisofolic acid: structure given in first source
(5)n,(8)n-deaza-(10)-n-methylfolate(5)N,(8)N-deaza-(10)-N-methylfolate: structure