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 QARS1.
Catalyzed reaction Glutamine–RNA ligase (EC 6.1.1.18) is an enzyme that catalyzes the chemical reaction ATP + L-glutamine + tRNAGln ⇌ {\displaystyle \rightleftharpoons } AMP + diphosphate + L-glutaminyl-tRNAGln The 3 substrates of this enzyme are ATP, L-glutamine, and tRNAGln, whereas its 3 products are AMP, diphosphate, and L-glutaminyl-tRNAGln. 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:tRNAGln 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-tRNAGln 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 tRNAGln with glutamate. Glutamine-tRNAGln is then formed by transamidation of the misacylated glutamate-tRNAGln 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 100 Å long. At the N-terminus, it has its catalytic active site with a Rossmann dinucleotide fold interacting with the 2′ OH of the final nucleotide of tRNAGln (A76), while the C-terminus interacts with the tRNAs anti-codon loop. The human glutaminyl-tRNA synthetase structure at N-terminus contains a two tandem nonspecific 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 nonviral protein:RNA complex. The purified enzyme was crystallized in complex with in vivo overexpressed tRNAGln. As of late 2024, over 38 structures have been solved for this class of enzymes. Some of the PDB accession codes include PDB: 1EUQ, PDB: 1EUY, PDB: 1EXD, PDB: 1GSG, PDB: 1GTR, PDB: 1GTS, PDB: 1NYL, PDB: 1O0B, PDB: 1O0C, PDB: 1QRS, PDB: 1QRT, PDB: 1QRU, PDB: 1QTQ, PDB: 1ZJW, and PDB: 2HZ7. The E. coli glutaminyl-tRNA synethetase structure complexed with its cognate tRNA, tRNAGln is depicted in the figure (accession number 1EUG.
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