| Ec Number: | 6.1.1.18 |
| Cas Number: | 9075-59-6 |
| Go Code: | 0004819 |
| 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.[1]
This enzyme participates in glutamate metabolism and aminoacyl-trna biosynthesis.
The human gene for glutaminyl-tRNA synthetase is QARS.
Glutamine—tRNA ligase is an enzyme that catalyzes the chemical reaction
ATP + L-glutamine + tRNAGln
\rightleftharpoons
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:[2]
In the eukaryotic cytoplasm and in some bacteria such as E. coli, glutaminyl-tRNA synthetase catalyzes glutamine-tRNAGln formation.[3] 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.[4] It is believed that glutaminyl-tRNA synethetases have evolved from the glutamyl-tRNA synthetase enzyme.[5]
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.
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 tRNAGln (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.[6]
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).[7] This was also the first crystal structure of a non-viral protein:RNA complex.[8] The purified enzyme was crystalized in complex with in vivo overexpressed tRNAGln.
As of late 2024, over 38 structures have been solved for this class of enzymes.[9] Some of the PDB accession codes include,,,,,,,,,,,,,, and . The E. coli glutaminyl-tRNA synethetase structure complexed with its cognate tRNA, tRNAGln is depicted in the figure (accession number 1EUG.[10]