ArticleJournal of bacteriology2008
Functional analysis of the Mycobacterium tuberculosis FAD-dependent thymidylate synthase, ThyX, reveals new amino acid residues contributing to an extended ThyX motif.
Article in Journal of bacteriology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 33 citations in OpenAlex.
- Bacterial origins of thymidylate metabolism in Asgard archaea and Eukarya.Nature communications · 2023Article
- Synthesis and Structure-Activity Relationship Studies of Pyrido [1,2-Molecules (Basel, Switzerland) · 2022Article
- Mechanism of Naphthoquinone Selectivity of Thymidylate Synthase ThyX.Biophysical journal · 2020Article
- Analysis of mutations leading to para-aminosalicylic acid resistance in Mycobacterium tuberculosis.Scientific reports · 2019Article
- A comparative analysis of methylome profiles of Campylobacter jejuni sheep abortion isolate and gastroenteric strains using PacBio data.Frontiers in microbiology · 2014Article
- Article
- Folate binding site of flavin-dependent thymidylate synthase.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Mechanisms and inhibition of uracil methylating enzymes.Bioorganic chemistry · 2012Review
- Mycobacterium tuberculosis thymidylate synthase gene thyX is essential and potentially bifunctional, while thyA deletion confers resistance to p-aminosalicylic acid.Microbiology (Reading, England) · 2012Article
- Direct contacts between conserved motifs of different subunits provide major contribution to active site organization in human and mycobacterial dUTPases.FEBS letters · 2010Article
- Flavin-dependent thymidylate synthase: a novel pathway towards thymine.Archives of biochemistry and biophysics · 2010Article
- Oxidase activity of a flavin-dependent thymidylate synthase.The FEBS journal · 2009Article
- Kinetics and ligand-binding preferences of Mycobacterium tuberculosis thymidylate synthases, ThyA and ThyX.PloS one · 2008Article
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A novel FAD-dependent thymidylate synthase, ThyX, is present in a variety of eubacteria and archaea, including the mycobacteria. A short motif found in all thyX genes, RHRX(7-8)S, has been identified. The three-dimensional structure of the Mycobacterium tuberculosis ThyX enzyme has been solved. Building upon this information, we used directed mutagenesis to produce 67 mutants of the M. tuberculosis thyX gene. Each enzyme was assayed to determine its ability to complement the defect in thymidine biosynthesis in a delta thyA strain of Escherichia coli. Enzymes from selected strains were then tested in vitro for their ability to catalyze the oxidation of NADPH and the release of a proton from position 5 of the pyrimidine ring of dUMP. The results defined an extended motif of amino acids essential to enzyme activity in M. tuberculosis (Y44X(24)H69X(25)R95HRX(7)S105XRYX(90)R199 [with the underlined histidine acting as the catalytic residue and the underlined serine as the nucleophile]) and provided insight into the ThyX reaction mechanism. ThyX is found in a variety of bacterial pathogens but is absent in humans, which depend upon an unrelated thymidylate synthase, ThyA. Therefore, ThyX is a potential target for development of antibacterial drugs.
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