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Glutamine—tRNA ligase
Crystal structure of E. coli glutaminyl-tRNA synthetase complexed with a tRNA(Gln) mutant and an active-site inhibitor (Accession number: 1EUG). The tRNA is depicted in green and the glutaminyl-tRNA synthetase is in orange.
Identifiers
EC no.	6.1.1.18
CAS no.	9075-59-6
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / QuickGO
Search PMC articles PubMed articles NCBI proteins

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 ${\displaystyle \rightleftharpoons }$ AMP + diphosphate + L-glutaminyl-tRNA

The 3 substrates of this enzyme are ATP, L-glutamine, and tRNA, whereas its 3 products are AMP, diphosphate, and L-glutaminyl-tRNA. 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 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 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 with glutamate. Glutamine-tRNA is then formed by transamidation of the misacylated glutamate-tRNA 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 (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.

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 is depicted in the figure (accession number 1EUG.

References

1. ^ Perona JJ (2013). "Glutaminyl-tRNA Synthetases". Madame Curie Bioscience Database . Landes Bioscience. Retrieved 2024-07-31.
2. "ExplorEnz: EC 6.1.1.18". www.enzyme-database.org. Retrieved 2024-08-05.
3. ^ Ibba M, Becker HD, Stathopoulos C, Tumbula DL, Söll D (July 2000). "The Adaptor hypothesis revisited". Trends in Biochemical Sciences. 25 (7): 311–316. doi:10.1016/s0968-0004(00)01600-5. ISSN 0968-0004. PMID 10871880.
4. ^ Rubio Gomez MA, Ibba M (August 2020). "Aminoacyl-tRNA synthetases". RNA. 26 (8): 910–936. doi:10.1261/rna.071720.119. PMC 7373986. PMID 32303649.
5. Woese CR, Olsen GJ, Ibba M, Söll D (March 2000). "Aminoacyl-tRNA Synthetases, the Genetic Code, and the Evolutionary Process". Microbiology and Molecular Biology Reviews. 64 (1): 202–236. doi:10.1128/MMBR.64.1.202-236.2000. ISSN 1092-2172. PMC 98992. PMID 10704480.
6. "Glutamine--tRNA ligase". InterPro. P47897.
7. Rould MA, Perona JJ, Söll D, Steitz TA (December 1989). "Structure of E. coli glutaminyl-tRNA synthetase complexed with tRNA(Gln) and ATP at 2.8 A resolution". Science. 246 (4934): 1135–1142. doi:10.1126/science.2479982. PMID 2479982.
8. PDB Statistics: Protein-Nucleic Acid Complexes Released Per Year Protein Data Bank
9. "InterPro". www.ebi.ac.uk. Retrieved 2024-08-02.
10. Sherlin LD, Bullock TL, Newberry KJ, Lipman RS, Hou YM, Beijer B, et al. (June 2000). "Influence of transfer RNA tertiary structure on aminoacylation efficiency by glutaminyl and cysteinyl-tRNA synthetases". Journal of Molecular Biology. 299 (2): 431–446. doi:10.1006/jmbi.2000.3749. PMID 10860750.

• Biology

• EC 6.1.1
• Enzymes of known structure