Disease relevance of THR4

• Comparison of the amino acid sequence of Bacillus subtilis threonine synthase with the National Biomedical Research Foundation protein sequence library revealed a statistically significant extent of similarity between the sequence of the tryptophan synthase beta chain from various organisms and that of threonine synthase [1].

High impact information on THR4

• In some genetic backgrounds, raa leu2 and raa thr4 double mutants are inviable, even on rich medium [2].
• Threonine synthase catalyzes the final step of threonine biosynthesis, the pyridoxal 5'-phosphate (PLP)-dependent conversion of O-phosphohomoserine into threonine and inorganic phosphate [3].
• Based on structural alignments with related enzymes, an enzyme-substrate complex was modeled into the active site of yeast threonine synthase, which revealed essentials for substrate binding and catalysis [3].
• Nucleotide sequence of the yeast THR4 gene encoding threonine synthase [4].
• The plasmid contains a 7.5-kb insert from the middle of the right arm of chromosome III, including the gene THR4 [5].

Biological context of THR4

• Analysis of the THR4 region on chromosome III of the yeast Saccharomyces cerevisiae [6].
• About 130 bp downstream of the THR4 gene another large open reading frame (563 amino acids) is found in the opposite orientation [6].
• This may imply that this open reading frame, called CTR86, shares a terminator region with THR4 [6].
• Using these plasmids only very weak complementation of a S. cerevisiae thr4 mutation was observed [7].
• Plasmid vectors that incorporate sequence elements from the dehydrofolate reductase-thymidylate synthase (DHFR-TS) locus of Toxoplasma gondii integrate into the parasite genome with remarkably high frequency (>1% of transfected parasites) [8].

Associations of THR4 with chemical compounds

• The gene encoding threonine synthase (THR4) from the yeast Saccharomyces cerevisiae was cloned by complementation of a thr4 mutant [6].
• These vectors may-but need not-include mutant DHFR-TS alleles that confer pyrimethamine resistance to transgenic parasites [8].
• Upon TS inhibition, dUTP pools may accumulate, inducing repeated cycles of uracil misincorporation into DNA and repair-mediated DNA damage [9].

References