Glutamine—tRNA ligase
| 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 | ||||||||
| |||||||||
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.
Catalyzed reaction
[edit]
Glutamine—tRNA ligase (EC 6.1.1.18) is an enzyme that catalyzes the chemical reaction
- ATP + L-glutamine + tRNAGln 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
[edit]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]
- glutaminyl-transfer RNA synthetase,
- glutaminyl-transfer ribonucleate synthetase,
- glutamine-tRNA synthetase, and
- glutamate-tRNA ligase
Evolution
[edit]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.[3] 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.[4] Glutaminyl-tRNA synthetase belongs to the class-I aminoacyl-tRNA synthetase family.
Structure
[edit]Of the glutaminyl-tRNA synthetases, the enzyme from E. coli is the most well studied structurally and biochemically.[1] 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.[1] 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 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, tRNAGln is depicted in the figure (accession number 1EUG.[10]
References
[edit]- ^ a b c Perona JJ (2013). "Glutaminyl-tRNA Synthetases". Madame Curie Bioscience Database [Internet]. Landes Bioscience. Retrieved 2024-07-31.
- ^ "ExplorEnz: EC 6.1.1.18". www.enzyme-database.org. Retrieved 2024-08-05.
- ^ a b 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.
- ^ a b 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.
- ^ 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.
- ^ "Glutamine--tRNA ligase". InterPro. P47897.
- ^ 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.
- ^ PDB Statistics: Protein-Nucleic Acid Complexes Released Per Year Protein Data Bank
- ^ "InterPro". www.ebi.ac.uk. Retrieved 2024-08-02.
- ^ 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.
