• dTMP kinase) catalyzes the phosphorylation of thymidine 5'-monophosphate (dTMP) to form thymidine 5'-diphosphate (dTDP) in the presence of ATP and magnesium: ATP + thymidine 5'-phosphate ⇌ {\displaystyle \rightleftharpoons } ADP + thymidine 5'-diphosphate Thymidylate kinase is a ubiquitous enzyme of about 25 Kd and is important in the dTTP synthesis pathway for DNA synthesis. (wikipedia.org)
  • Thymidylate kinase's subfamily is predicted thymidylate kinase, TKRP1. (wikipedia.org)
  • The present study evaluated the prognostic value of the epidermal growth factor receptor (EGFR) mutation status, and excision repair cross-complementation group 1 (ERCC1) and thymidylate synthase (TS) expression following intercalated tyrosine kinase inhibitor (TKI) therapy and platinum- and pemetrexed-based chemotherapies (subsequent second-line treatment) for patients with adenocarcinoma non-small-cell lung cancer (AC-NSCLC). (medsci.org)
  • Human herpesvirus 8 open reading frame 21 is a thymidine and thymidylate kinase of narrow substrate specificity that efficiently phosphorylates zidovudine but not ganciclovir. (umassmed.edu)
  • Impairment of thymidylate (dTMP) biosynthesis severely diminishes the viability of parasitic protozoa and the absence of enzymatic activities specifically involved in the formation of dTMP (e.g. dUTPase, thymidylate synthase, dihydrofolate reductase or thymidine kinase) results in decreased deoxythymidine triphosphate (dTTP) levels and the so-called thymineless death. (eurekaselect.com)
  • Mycobacterium tuberculosis thymidylate kinase: structural studies of intermediates along the reaction pathway. (hal.science)
  • Mycobacterial thymidylate kinase (TMKmyc) is a phosphotransferase critical for the synthesis of the thymidine triphosphate precursor necessary for M. tb DNA synthesis. (biomedcentral.com)
  • Therefore, molecular docking was also used in the present study to simulate the binding of cordycepin with different antibacterial targets, such as β-ketoacyl-(acyl-carrier-protein) synthase III (FabH), DNA gyrase B and thymidylate kinase, in order to identify the most likely antimicrobial mechanism of cordycepin. (spandidos-publications.com)
  • Decreased expression of six RNA species was seen at various time points in all cell strains analyzed, these were: plasminogen activator (PLAT), centromere protein F (CPF), replication factor C (RFC3), thymidylate synthetase (TYMS), a putative mitotic checkpoint kinase (BUB1) and a gene of unknown function (GenBank accession number AI859865). (cdc.gov)
  • Thymidylate synthase inhibitors. (nih.gov)
  • Thymidylate synthase is vital for de novo DNA synthesis, by catalyzing the transformation of deoxy-uridine monophosphate (dUMP) to deoxy-thymidine monophosphate (dTMP). (careersfromscience.org)
  • Thymidylate synthase (TS) catalyzes the reductive methylation of deoxyuridine monophosphate (dUMP) by 5, 10-methylenetetrahydrofolate (CH2H4folate) to form deoxythymidine monophosphate (dTMP) and dihydrofolate (H2folate). (rcsb.org)
  • The phenotypes of single- (SKO) and double-knockout (DKO) lines of dihydrofolate reductase-thymidylate synthase (DHFR-TS) of bloodstream Trypanosoma brucei were evaluated in vitro and in vivo. (dundee.ac.uk)
  • Cancer drugs such as 5-fluorouracil (5-FU) that target the enzyme thymidylate synthase (TS) have been and are still being widely used in cancer treatment, but as with other anti-cancer drugs, the majority of tumors do not respond to the treatment, whereas the patients still suffer drug-related toxicity. (imrpress.com)
  • Drugs that target human thymidylate synthase (hTS), a dimeric enzyme, are widely used in anticancer therapy. (unife.it)
  • The deubiquitinating enzyme UCHL1 promotes resistance to pemetrexed in non-small cell lung cancer by upregulating thymidylate synthase. (bvsalud.org)
  • Pemetrexed is an antimetabolic agent and is well-known as a potent inhibitor of thymidylate synthase (TS). (scirp.org)
  • The cPs were screened for the ability to inhibit recombinant human thymidylate synthase (hTS), and peptide 7 was found to act as an allosteric inhibitor more potent than its parent open-chain peptide [Pro3]LR. (unipv.it)
  • Here, we review the available literature in relation to drug discovery studies targeting thymidylate biosynthesis in kinetoplastid (genera Trypanosoma and Leishmania) and apicomplexan (Plasmodium spp and Toxoplasma gondii) protozoans. (eurekaselect.com)
  • Specificity: This antibody recognizes a protein of 36kDa, identified as Thymidylate Synthase (TS) (EC 2.1.1.45). (scytek.com)
  • Several biomarkers have been used to predict treatment responses, such as the EGFR mutation status for targeted therapy or the excision repair cross-complementation group 1 (ERCC1) and thymidylate synthase (TS) expression for conventional chemotherapy [ 3 - 8 ]. (medsci.org)
  • We investigated the clinical significance of E2F1 gene expression in relation to its target genes, thymidylate synthase ( TS ) and Survivin , in case of non-small-cell lung cancer (NSCLC). (aacrjournals.org)
  • Here we illustrate the ability of human CMV (HCMV) to stimulate cellular thymidylate synthase (TS) gene expression in quiescent human embryonic lung fibroblasts. (elsevierpure.com)
  • Mechanistically, UCHL1 promoted PEM resistance in NSCLC by upregulating the expression of thymidylate synthase (TS), based on reduced TS expression after UCHL1 inhibition and re-emergence of PEM resistance upon TS restoration. (bvsalud.org)
  • A prospective, blinded analysis of thymidylate synthase and p53 expression as prognostic markers in the adjuvant treatment of colorectal cancer. (ox.ac.uk)
  • Thymidylate synthase (TS) is a target for pemetrexed and the prodrug 5-fluorouracil (5-FU) that inhibit the protein by binding at its active site. (unimore.it)
  • Landis, D.M., Heindel, C.C. and Loeb, L.A. (2001) Creation and Characterization of 5-Fluorodeoxyuridine-Resistant Arg50 Loop Mutants of Human Thymidylate Synthase. (scirp.org)
  • A naturally occurring variation in thymidylate synthase structure is associated with a reduced response to 5-fluoro-2'-deoxyuridine in a human colon tumor cell line. (aspetjournals.org)
  • Human and other mammalian thymidylate synthase (TS) enzymes have an N-terminal extension of approximately 27 amino acids that is not present in bacterial TSs. (rcsb.org)
  • Thymidylate synthase (TS) is a prominent drug target for different cancer types. (unipv.it)
  • Inhibition of thymidylate synthase (TS) is an important mechanism of action of fluoropyrimidine antimetabolites. (aspetjournals.org)
  • BACKGROUND: Despite previous studies, uncertainty has persisted about the role of thymidylate synthase (TS) and p53 status as markers of prognosis in colorectal cancer (CRC). (ox.ac.uk)
  • Amino acids in the dihydrofolate reductase thymidylate synthase gene of P. falciparum involved in pyrimethamine resistance. (ajtmh.org)
  • Understanding the structural basis of species selective, stereospecific inhibition for Cryptosporidium and human thymidylate synthase. (cornell.edu)
  • Thymidylate synthases (Thy) are key enzymes in the synthesis of deoxythymidylate, 1 of the 4 building blocks of DNA. (tau.ac.il)
  • TS (thymidylate synthase), MSI (microsatellite instability), DPD (dihydropyrimidine dehydrogenase). (empr.com)
  • Quantitative measurement of thymidylate synthase and dihydropyrimidine dehydrogenase mRNA level in gastric cancer by real-time RT-PCR. (koreamed.org)
  • Induction of resistance to the multitargeted antifolate Pemetrexed (ALIMTA) in WiDr human colon cancer cells is associated with thymidylate synthase overexpression. (amsterdamumc.org)
  • Using immunohistochemistry to evaluate thymidylate synthase protein levels, we found that the expression of thymidylate synthase in these mixed tumors roughly parallel that of squamous cell carcinoma, instead of falling in between squamous cell and adenocarcinoma. (njit.edu)
  • The thymidylate synthase (TS), an important target for many anticancer drugs, has been cloned from different species. (elsevierpure.com)
  • Thymidylate synthase expression is known to be higher in squamous cell carcinoma than in adenocarcinoma of the lung. (njit.edu)
  • However, there is limited data on thymidylate synthase expression in adenosquamous carcinoma, a distinct subtype of lung cancer containing both squamous and glandular differentiation. (njit.edu)
  • Of note, in adenosquamous samples, the expression of thymidylate synthase was more closely correlated within the two components than would be expected by random chance alone. (njit.edu)
  • Given the similarity of thymidylate synthase expression between squamous cell and adenosquamous carcinoma, and that thymidylate synthase is the main target of pemetrexed, we extrapolate that pemetrexed may also have inferior clinical activity in adenosquamous carcinoma. (njit.edu)
  • A prospective, blinded analysis of thymidylate synthase and p53 expression as prognostic markers in the adjuvant treatment of colorectal cancer. (ox.ac.uk)
  • The quantitation by radioimmunoassay of 2'-deoxyuridine 5'-triphosphate in extracts of thymidylate synthase-inhibited cells. (ox.ac.uk)
  • The crystal structures of a deletion mutant of human thymidylate synthase (TS) and its ternary complex with dUMP and Tomudex have been determined at 2.0 A and 2.5 A resolution, respectively. (rcsb.org)
  • Raltitrexed selectively inhibits thymidylate synthase and therefore prevents DNA replication. (ispub.com)
  • Patients with lower levels thymidylate synthase had better treatment outcomes with pemetrexed-based chemotherapy. (survivingmesothelioma.com)
  • Wahba NI, Khorsid O, Abo Elkasem F, Bahnassy A, Gaafer R. The Predictive Value of ERCC1, RRM1, and Thymidylate Synthase in Advanced Malignant Pleural Mesothelioma Patients Treated with Platinum-Based Chemotherapy. (survivingmesothelioma.com)
  • Germline thymidylate synthase deficiency impacts nucleotide metabolism and causes dyskeratosis congenita. (cdc.gov)
  • BACKGROUND: Despite previous studies, uncertainty has persisted about the role of thymidylate synthase (TS) and p53 status as markers of prognosis in colorectal cancer (CRC). (ox.ac.uk)
  • If a doctor wants to start chemotherapy with pemetrexed, they might want to test levels of thymidylate synthase in the patient. (survivingmesothelioma.com)