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 glutamine amino acid onto its cognate tRNA.^[1]

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

The human gene for glutaminyl-tRNA synthetase is QARS.

A glutamine—tRNA ligase (EC 6.1.1.18) is an enzyme that catalyzes the chemical reaction

ATP + L-glutamine + tRNA^Gln ${\displaystyle \rightleftharpoons }$ 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 is shown in the figure for the aaRS cycle.

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). Other names in use include:

• glutaminyl-tRNA synthetase,
• glutaminyl-transfer RNA synthetase,
• glutaminyl-transfer ribonucleate synthetase,
• glutamine-tRNA synthetase,
• glutamine translase,
• glutamate-tRNA ligase,
• glutaminyl ribonucleic acid, and
• GlnRS.

Although present in eukaryotes, glutaminyl-tRNA synthetase is absent from many prokaryotes, mitochondria, and chloroplasts, in which Gln-tRNA^Gln is formed by transamidation of the misacylated Glu-tRNA^Gln by the glutaminyl-tRNA synthase (glutamine-hydrolysing) enzyme.^[2]

Aminoacyl tRNA synthetases are divided into two major classes based on their active site structure: class I and II.^[2] Glutaminyl-tRNA synthetase belongs to the class-I aminoacyl-tRNA synthetase family.

Starting at the N-terminus, the human glutaminyl-tRNA synthetase contains a two tandem non-specific RNA binding regions, a catalytic domain, and two tandem anti-codon binding domains in the C-terminus.^[3]

The first crystal structure of a tRNA synthetase in complex with its cognate tRNA was that of tRNA-Gln:GlnRS, determined in 1989 (PDB accession code (1GSG). ^[4] This was also the first crystal structure of a non-viral protein:RNA complex.^[5]

As of late 2024, over 38 structures have been solved for this class of enzymes.^[6] 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. ^[7]