Glutamine—tRNA ligase

Template:Cs1 config Template:Infobox enzyme Glutamine—tRNA ligase or glutaminyl-tRNA synthetase (GlnRS) is an aminoacyl-tRNA synthetase (aaRS or ARS), also called tRNA-ligase. is an enzyme that attaches the amino acid glutamine onto its cognate tRNA.

This enzyme participates in glutamate metabolism and aminoacyl-trna biosynthesis.

The human gene for glutaminyl-tRNA synthetase is QARS.

Catalyzed reaction

The cycle and mechanism of aminoacylation by tRNA synthetases.

Glutamine—tRNA ligase (Template:EnzExplorer) is an enzyme that catalyzes the chemical reaction

ATP + L-glutamine + tRNA^Gln $\rightleftharpoons$ AMP + diphosphate + L-glutaminyl-tRNA^Gln

The 3 substrates of this enzyme are ATP, L-glutamine, and tRNA^Gln, whereas its 3 products are AMP, diphosphate, and L-glutaminyl-tRNA^Gln. The cycle of aminoacylation reaction is shown in the figure.

Nomenclature

This enzyme belongs to the family of ligases, to be specific those forming carbon-oxygen bonds in aminoacyl-tRNA and related compounds. The systematic name of this enzyme class is L-glutamine:tRNA^Gln ligase (AMP-forming). Glutaminyl-tRNA synthetase or GlnRS is the primary name in use in the scientific literature. Other names that have been reported are:

• glutaminyl-transfer RNA synthetase,
• glutaminyl-transfer ribonucleate synthetase,
• glutamine-tRNA synthetase, and
• glutamate-tRNA ligase

Evolution

In the eukaryotic cytoplasm and in some bacteria such as E. coli, glutaminyl-tRNA synthetase catalyzes glutamine-tRNA^Gln formation. However a two-step formation process is necessary for its formation in all archaebacteria and most eubacteria as well as most eukaryotic organelles. In these cases, a glutamyl-tRNA synthetase first mis-aminoacylates tRNA^Gln with glutamate. Glutamine-tRNA^Gln is then formed by transamidation of the misacylated glutamate-tRNA^Gln by the glutaminyl-tRNA synthase (glutamine-hydrolysing) enzyme. It is believed that glutaminyl-tRNA synethetases have evolved from the glutamyl-tRNA synthetase enzyme.

Aminoacyl tRNA synthetases are divided into two major classes based on their active site structure: class I and II. Glutaminyl-tRNA synthetase belongs to the class-I aminoacyl-tRNA synthetase family.

Structure

Of the glutaminyl-tRNA synthetases, the enzyme from E. coli is the most well studied structurally and biochemically. It is 553 amino acids long and is about 100Å long. At the N-terminus, it has its catalytic active site with a Rossmann di-nucleotide fold interacting with the 2'OH of the final nucleotide of tRNA^Gln (A76), while the C terminus interacts with the tRNA's anti-codon loop. The human human glutaminyl-tRNA synthetase structure at N-terminus contains a two tandem non-specific RNA binding regions, a catalytic domain, and two tandem anti-codon binding domains in the C-terminus.

The first crystal structure of a tRNA synthetase in complex with its cognate tRNA was that of the E. coli tRNA-Gln:GlnRS, determined in 1989 (PDB accession code (1GSG). This was also the first crystal structure of a non-viral protein:RNA complex. The purified enzyme was crystalized in complex with in vivo overexpressed tRNA^Gln.

As of late 2024, over 38 structures have been solved for this class of enzymes. Some of the PDB accession codes include Template:PDB link, Template:PDB link, Template:PDB link, Template:PDB link, Template:PDB link, Template:PDB link, Template:PDB link, Template:PDB link, Template:PDB link, Template:PDB link, Template:PDB link, Template:PDB link, Template:PDB link, Template:PDB link, and Template:PDB link. The E. coli glutaminyl-tRNA synethetase structure complexed with its cognate tRNA, tRNA^Gln is depicted in the figure (accession number 1EUG.