An alternative flavin-dependent mechanism for thymidylate synthesis

Hannu Myllykallio 1 Gérard Lipowski 2 D Leduc 1 Jonathan Filee 1 Patrick Forterre 1 Ursula Liebl 2
1 IGM - Institut de génétique et microbiologie [Orsay]
2 LOB - Laboratoire d'optique et biosciences
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.
Document type :
Journal articles
Complete list of metadatas
https://hal-polytechnique.archives-ouvertes.fr/hal-00836930
Contributor : Denis Roura <>
Submitted on : Tuesday, June 25, 2013 - 3:37:55 PM
Last modification on : Thursday, February 7, 2019 - 2:30:27 PM

Identifiers

Collections

X-LOB | X | PARISTECH | I2BC | X-DEP-BIO

Citation

Hannu Myllykallio, Gérard Lipowski, D Leduc, Jonathan Filee, Patrick Forterre, et al.. An alternative flavin-dependent mechanism for thymidylate synthesis. Science, American Association for the Advancement of Science, 2002, 297 (5578), pp.105. ⟨10.1126/science.1072113⟩. ⟨hal-00836930⟩

Export

BibTeX TEI DC DCterms EndNote

Share

Metrics

Record views

126

Contact

support.ccsd.cnrs.fr
hal.support@ccsd.cnrs.fr
Logo CCSD