PMID:12029065
| Citation |
Myllykallio, H, Lipowski, G, Leduc, D, Filee, J, Forterre, P and Liebl, U (2002) An alternative flavin-dependent mechanism for thymidylate synthesis. Science 297:105-7 |
|---|---|
| Abstract |
Although deoxythymidylate cannot be provided directly by ribonucleotide reductase, the gene encoding thymidylate synthase ThyA is absent from the genomes of a large number of nonsymbiotic microbes. We show that ThyX (Thy1) proteins of previously unknown function form a large and distinct class of thymidylate synthases. ThyX has a wide but sporadic phylogenetic distribution, almost exclusively limited to microbial genomes lacking thyA. ThyX and ThyA use different reductive mechanisms, because ThyX activity is dependent on reduced flavin nucleotides. Our findings reveal complexity in the evolution of thymidine in present-day DNA. Because ThyX proteins are found in many pathogenic microbes, they present a previously uncharacterized target for antimicrobial compounds. |
| Links |
PubMed Online version:10.1126/science.1072113 |
| Keywords |
Catalysis; Deoxyuracil Nucleotides/metabolism; Electron Transport; Escherichia coli/enzymology; Escherichia coli/genetics; Escherichia coli/growth & development; Flavin Mononucleotide/metabolism; Flavin-Adenine Dinucleotide/metabolism; Gene Transfer, Horizontal; Genes, Archaeal; Genes, Bacterial; Helicobacter pylori/enzymology; Helicobacter pylori/genetics; Molecular Weight; Phylogeny; Pyrococcus/enzymology; Pyrococcus/genetics; Recombinant Proteins/metabolism; Tetrahydrofolates/metabolism; Thymidine Monophosphate/biosynthesis; Thymidylate Synthase/chemistry; Thymidylate Synthase/genetics; Thymidylate Synthase/isolation & purification; Thymidylate Synthase/metabolism; Transformation, Bacterial; Uridine Monophosphate/metabolism |
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