What does thymidylate synthase do?
Thymidylate synthase plays a central role in the biosynthesis of thymidylate, an essential precursor for DNA biosynthesis. In addition to its role in catalysis and cellular metabolism, studies from our laboratory have shown that thymidylate synthase functions as an RNA binding protein.
What is thymidylate synthesis?
Thymidylate synthesis occurs at a greater rate during DNA replication when cells are in S-phase of the cell cycle. De novo thymidylate biosynthesis is impaired by folate or vitamin B12 deficiency. Impaired de novo thymidylate biosynthesis causes uracil misincorporation into DNA and DNA instability.
What is the cofactor of thymidylate synthase?
4.1 Thymidylate synthase SHMT catalyzes the formation of 5,10-methylenetetrahydrofolate from tetrahydrofolate (THF), coupled with the conversion of serine into glycine, with pyridoxal phosphate (PLP) as a cofactor.
What are the products of thymidylate synthase reaction?
Thymidylate synthase (TS) (EC 2.1. 1.45) is an enzyme that catalyzes the conversion of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP). Thymidine is one of the nucleotides in DNA.
What is the difference between thymine and thymidine?
The key difference between thymine and thymidine is that thymine is a nucleobase, whereas thymidine is a nucleoside. A nucleotide contains a nucleobase, sugar molecule and a phosphate group. The combination of a nucleobase with a sugar forms a nucleoside.
What is the substrate for thymidylate synthase?
In the proposed mechanism, TS forms a covalent bond to the substrate dUMP through a 1,4-addition involving a cysteine nucleophile. The substrate tetrahydrofolate donates a methyl group to the alpha carbon while reducing the new methyl on dUMP to form dTMP.
What is the function of thymidine?
Thymidine kinase or deoxyribonucleoside kinase (TK) catalyzes the conversion of deoxythymidine (THM) to deoxythymidine 5′-phosphate (THMP) with the conversion of ATP to ADP. TK has an important role in the synthesis of DNA. It is required for the action of many antiviral drugs. Higher organisms have 2 isozymes.
What is thymine easy definition?
: a pyrimidine base C5H6N2O2 that is one of the four bases coding genetic information in the polynucleotide chain of DNA — compare adenine, cytosine, guanine, uracil.
Which is a potent inhibitor of thymidylate synthase?
The antipyrimidine drug, 5-fluorouracil (5-FU), as its active metabolite, FdUMP, is a potent inhibitor of thymidylate synthase (TS), and this is generally considered to be its primary mechanism of action (Pratt et al., 1994).
What is the coenzyme for thymidylate synthase?
(c) Thymidylate synthetase inhibitors The methylation of the uracil moiety (present in RNA) to 5-methyl uracil (thymine, present in DNA) requires participation of a folic acid coenzyme, N5, N10-methylenetetrahydrofolate as a methyl donor.
What does viral thymidine kinase do?
Thymidine kinase (TK) activity is measured by radioenzymatic assay. TK is an enzyme that catalyses the phosphorylation of deoxythymidine to deoxythymidine monophosphate. Its activity is highest in G1-S translation checkpoint and then declines rapidly in the G2 phase of the cell cycle.
What are TK levels?
Objective: Serum thymidine kinase (TK) levels have been shown to be correlated with survival in many malignancies, including chronic lymphocytic leukaemia (CLL). This study was designed to investigate associations between TK levels and other prognostic markers, in newly and previously diagnosed Binet stage A patients.
What kind of enzyme is thymidylate synthase ( TS )?
Thymidylate synthase (TS) (EC 2.1.1.45) is an enzyme that catalyzes the conversion of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP).
Why is thymidylate synthase important to normal DNA replication?
The enzyme is essential for regulating the balanced supply of the 4 DNA precursors in normal DNA replication: defects in the enzyme activity affecting the regulation process cause various biological and genetic abnormalities, such as thymineless death. The enzyme is an important target for certain chemotherapeutic drugs.
Which is a reductive methylation of thymidylate 5 ′ monophosphate?
Thymidylate synthase is a folate-dependent enzyme that catalyzes the reductive methylation of 2′-deoxyuridine-5′-monophosphate (dUMP) by the reduced folate 5,10-methylenetetrahydrofolate (CH2THF) to 2′-deoxythymidine-5′-monophosphate (dTMP, thymidylate) and dihydrofolate.
How does tetrahydrofolate contribute to thymidylate synthase?
The substrate tetrahydrofolate donates a methyl group to the alpha carbon while reducing the new methyl on dUMP to form dTMP. This shows the intricate interactions of the UMP in the active site of thymidylate synthase.