Disease relevance of GLN4

• The monomeric yeast Saccharomyces cerevisiae glutaminyl-tRNA synthetase, like several other class I eukaryote tRNA synthetases, has an active-site-containing 'body' that is closely homologous to its Escherichia coli relative, but is tagged at its N-terminus with a novel and dispensable appended domain whose role has been obscure [1].

High impact information on GLN4

• Two of them, GlnRS and AspRS, have been cocrystallized with their cognate tRNA [2].
• An exception is Gln-tRNA synthesis, which in eukaryotes is catalyzed by glutaminyl-tRNA synthetase (GlnRS), while most bacteria, archaea, and chloroplasts employ the transamidation pathway, in which a tRNA-dependent glutamate modification generates Gln-tRNA [3].
• We found no biochemical support for this in Saccharomyces cerevisiae mitochondria, but demonstrated the presence of the cytoplasmic GlnRS in the organelle and its involvement in mitochondrial Gln-tRNA synthesis [3].
• Because of differences between the yeast and E. coli glutamine tRNAs that presumably perturb the enzyme-tRNA interface, E. coli glutaminyl-tRNA synthetase does not charge yeast tRNA [1].
• We describe the nucleotide sequences of several overlapping cDNA clones specific for human glutaminyl-tRNA synthetase [4].

Biological context of GLN4

• Further experiments established that GLN4 is an essential gene that is located on chromosome XV [5].
• Cells which harbor such in-frame deletions on a multi copy plasmid are viable, even when a deletion construct is the only source of GLN4-encoded activity [6].
• The yeast GLN4 transcripts have 5' termini that start approximately 25 nucleotides in front of the long open reading frame [7].
• A multicopy recombinant plasmid with a 5-kilobase-pair genomic insert conferred sixfold elevation in glutaminyl-tRNA synthetase activity and restored a Gln+ phenotype to strains that were Gln- by virtue of a mutant gln4 allele [5].
• Likewise, examination of the global mode of motion of GlnRS in the complex indicates that residues 40 to 45, 260 to 270, 306 to 314, 320 to 327 and 478 to 485, all of which cluster near the ATP binding site, form a hinge-bending region controlling the cooperative motion, and thereby the catalytic function, of the enzyme [8].

Associations of GLN4 with chemical compounds

• Saccharomyces cerevisiae glutaminyl-tRNA synthetase mutants were isolated through systematic screening of tight Gln- derivatives of a leaky glutamine auxotroph [9].

Other interactions of GLN4

• Subfragments of the 5-kilobase insert directed integration of URA3 to GLN4 [5].

References