EC Number   |
General Information |
Reference |
|---|
   6.1.1.18 | evolution |
human GlnRS is a monomeric class I aminoacyl-tRNA synthetase family member |
745927 |
| 6.1.1.18 | evolution |
the architecture of the GlnRS RNP has differentiated over evolutionary time to maintain glutamine-binding affinity at a weak level, and provides strong evidence for long-distance communication |
716940 |
| 6.1.1.18 | evolution |
the enzyme belongs to the class I aminoacyl-tRNA synthetase family |
745576 |
| 6.1.1.18 | evolution |
the enzyme evolved by gene duplication in early eukaryotes from a nondiscriminating glutamyl-tRNAsynthetase (GluRSND, EC 6.1.1.24) that aminoacylates both tRNAGln and tRNAGlu with glutamate. This ancient GluRS also separately differentiated to exclude tRNAGln as a substrate, and the resulting discriminating GluRS and GlnRS further acquired additional protein domains assisting function in cis (the GlnRS N-terminal Yqey domain) or in trans (the Arc1p protein associating with GluRS), evolutionary modeling, detailed overview. These added domains are absent in contemporary bacterial GlnRS and GluRS. The eukaryote-specific protein domains substantially influence amino acid binding, tRNA binding and aminoacylation efficiency, but they play no role in either specific nucleotide readout or discrimination against noncognate tRNA. Eukaryotic tRNAGln and tRNAGlu recognition determinants are found in equivalent positions and aremutually exclusive to a significant degree, with key nucleotides located adjacent to portions of the protein structure that differentiated during the evolution of archaeal nondiscriminating GluRS to GlnRS. The added eukaryotic domains arose in response to distinctive selective pressures associated with the greater complexity of the eukaryotic translational apparatus. GluRS and GlnRS are among just four aaRS families (the others are arginyl-tRNA synthetase and class I LysRS) that require the presence of tRNA for synthesis of the aminoacyl adenylate reaction intermediate. Each cytoplasmic GlxRS-tRNA pair has fully lost the ancestral nondiscriminating activity in the course of coevolution, and the more stringent specificities of Saccharomyces cerevisiae GlnRS and GluRS arise from the conserved catalytic portions of each enzyme |
-, 745552 |
| 6.1.1.18 | malfunction |
heterozygous mutations in GlnRS cause severe brain disorders. Pathological mutations mapping in the N-terminal domain alter the domain structure, and decrease catalytic activity and stability of GlnRS, whereas missense mutations in the catalytic domain induce misfolding of the enzyme. The reduced catalytic efficiency and a propensity of GlnRS mutants to misfold trigger the disease development |
745927 |
| 6.1.1.18 | malfunction |
mutations in QARS, encoding glutaminyl-tRNA synthetase, cause progressive microcephaly, cerebral-cerebellar atrophy, and intractable seizures |
743985 |
| 6.1.1.18 | more |
analysis of the contributions to aminoacylation efficiency made by the N-terminal Yqey domain of Saccharomyces cerevisiae GlnRS. tRNA recognition determinants in the acceptor arm, at the 3'-anticodon position and in the globular core, overview |
-, 745552 |
| 6.1.1.18 | more |
generation of a comprehensive mapping of intramolecular communication in the glutaminyl-tRNA synthetase:tRNAGln complex, interaction analysis, detailed overview. Distinct coupling amplitudes for glutamine binding and aminoacyl-tRNA formation on the enzyme, respectively, implying the existence of multiple signaling pathways. Signaling from binding of the tRNA inner elbow, overview. Seven protein contacts with the distal tRNA vertical arm each weaken glutamine binding affinity across distances up to 40 A |
716940 |
| 6.1.1.18 | more |
in the multisynthetase complex (MSC) subcomplex (RQA1 subcomplex) comprising arginyl-tRNA synthetase (ArgRS), glutaminyl-tRNA synthetase (GlnRS), and the auxiliary factor aminoacyl tRNA synthetase complex-interacting multifunctional protein 1 ((AIMP1)/p43), the N-terminal domain of ArgRS forms a long coiled-coil structure with the N-terminal helix of AIMP1 and anchors the C-terminal core of GlnRS, thereby playing a central role in assembly of the three components. Mutation of AIMP1 destabilizes the N-terminal helix of ArgRS and abrogates its catalytic activity. The MSC complex is comprised of nine different aminoacyl-tRNA synthetases (ARSs) and three accessary proteins. Mutation of the N-terminal helix of ArgRS liberates GlnRS, which is known to control cell death. This ternary RQA1 complex is further anchores to AIMP2/p38 through interaction with AIMP1. Importance of interactions between the N-terminal domains of ArgRS and AIMP1 for the catalytic and noncatalytic activities of ArgRS and for the assembly of the higher-order MSC protein complex. The N-terminal domain of human GlnRS interacts with ArgRS in the MSC, GlnRS is anchored to the complex by the interaction of its C-terminal core with the Hb helix of ArgRS, structure-function analysis, overview. The RQA1 subcomplex also can form a hexameric structure |
746294 |
| 6.1.1.18 | more |
molecular dynamics modeling of L-GlnAMP using the PDB ID 1QTQ X-ray structure, superimposed based on their protein/tRNA environment, enzyme molecular dynamics simulation amd modeling, structure-function analysis, detailed overview |
745576 |
