Disease relevance of thyA

• This open reading frame is immediately 5' to the thyA gene and is allelic to umpA of Escherichia coli [1].
• The thymidylate synthetase gene of B. subtilis bacteriophage Phi-3-T, when cloned in plasmids pSC101 or pMB9 is expressed in E. coli [2].
• Genes encoding thymidylate synthetase from Bacillus subtilis bacteriophages were cloned in Escherichia coli [3].
• Synthetic inhibitors of Escherichia coli, calf thymus, and Ehrlich ascites tumor thymidylate synthetase [4].

High impact information on thyA

• These results suggest that certain folate analogues may be useful in distinguishing between a host and an infecting organism's thymidylate synthetase and could thus provide an additional means of screening for potential chemotherapeutic agents [5].
• The inhibitory action of folic acid oligoglutamates on E. coli thymidylate synthetase was subject to reversal with 0.4 M NaCl, an effect that was more marked with various pteroyloligoglutamates than with H4homopteroylmonoglutamate and N-5, N-8-deaza-N-10-methylpteroylmonoglutamate [6].
• Naturally occurring oligoglutamate derivatives of folic acid in extracts of Escherichia coli have been isolated on the basis of their inhibitory actions toward thymidylate synthetase and dihydrofolate reductase [6].
• Lysine analogs of N-5-formyl-H4folate containing alpha0glutamyl groups in peptide linkage to the epsilon-amino group of lysine were relatively poor inhibitors of thymidylate synthetase [6].
• It is concluded that the size of the 2'-substituent and not its polarity (and the concomitant conformational change) determines substrate specificity of thymidylate synthetase [7].

Chemical compound and disease context of thyA

• Isolation and partial characterization of a bacteriophage T5 mutant unable to induce thymidylate synthetase and its use in studying the effect of uracil incorporation into DNA on early gene expression [8].
• None of the enzymatically prepared tetrahydrohomopteroyl derivatives tested was as active as Nalpha-tetrahydrohomopteroyl glutamate (tetrahydrohomofolate) as an inhibitor of E. coli thymidylate synthetase [9].
• By infecting cells with the phage Mu-1 and isolating low-thymine-requiring derivatives of a strain lacking thymidylate synthetase and also thymidine-resistant mutants of a dra-strain, it has been possible to select for strains in which Mu-1 is inserted in this gene cluster [10].

Biological context of thyA

• The nucleotide sequence 5' to this dfr gene showed similarity to thymidylate synthetase genes, suggesting that the dfr and thy genes from E. faecalis are located in tandem [11].
• In a study of active site binding the inhibition of thymidylate synthetase derived from Escherichia coli, calf thymus, and Ehrlich ascites tumor was examined using eight inhibitors [4].

Associations of thyA with chemical compounds

• Nalpha-Tetrahydropteroyl-Nepsilon-(di-alpha-lysyl)lysine was the most active thymidylate synthetase substrate of the polylysine derivatives, being 67% as active as tetrahydrofolate [9].
• Thymidine incorporation into P. stutzeri was enhanced 12-fold more in mutants lacking thymidylate synthetase activity [12].
• Since this strain lacks thymidylate synthetase, it is unable to grow on minimal medium containing thymine [10].
• These results suggest that 5-FU may exert its SOS inducibility by inhibiting thymidylate synthetase and then disturbing DNA metabolism but not by incorporating 5-FU residues into RNA [13].
• The inducibility of the umuC gene by 5-FU, the metabolite of which inhibits thymidylate synthetase, was abolished in cultures containing deoxythymidine monophosphate which is converted from deoxyuridine monophosphate by thymidylate synthetase [13].

Analytical, diagnostic and therapeutic context of thyA

• Thymidylate synthetase was assayed in yeast cell lysates by high-pressure liquid chromatography to monitor the conversion of [6-3H]dUMP to [6-3H]dTMP [14].
• Molecular cloning and amplification of the gene for thymidylate synthetase of E. coli [15].
• Purification of thymidylate synthetase by means of affinity chromatography on tetrahydroamethopterin-aminoethyl-Sepharose [16].

References