# Glutamine—tRNA ligase

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

Glutamine—tRNA ligase (EC 6.1.1.18) 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 1EUQ, 1EUY, 1EXD, 1GSG, 1GTR, 1GTS, 1NYL, 1O0B, 1O0C, 1QRS, 1QRT, 1QRU, 1QTQ, 1ZJW, and 2HZ7. The E. coli glutaminyl-tRNA synethetase structure complexed with its cognate tRNA, tRNA$^{Gln}$ is depicted in the figure (accession number 1EUG.