EC Number   |
General Information |
Reference |
|---|
    6.1.1.2 | evolution |
an ancestral tryptophanyl-tRNA synthetase precursor achieves high catalytic rate enhancement without ordered ground-state tertiary structures. The TrpRS Urzyme catalytic activity arises neither from tiny amounts of wild-type enzyme, nor from a separate population of folded and highly active Urzyme molecules not in equilibrium with the general population. AaRS Urzymes lack much of the mass of modern aaRS, retaining only a small portion of the hydrophobic cores of the full-length enzymes. AaRS Urzymes contain 120-130 amino acids, and consist of little more than is required to form intact active sites. They retain over 60% of the transition-state stabilization free energy for amino acid activation and the ability to aminoacylate tRNA. Further, they preserve about 20% of the Gibbs energies necessary to discriminate between competing amino acid substrates and preferentially activate amino acids from within, rather than outside, their own class. A major fraction of TrpRS Urzyme molecules contribute to the rate acceleration by transiently forming tight transition-state complexes |
743913 |
| 6.1.1.2 | evolution |
the activation reaction mechanism of TrpRS from the basal eukaryote Gardia lamblia differs from that of higher eukaryotes, overview. The N-terminus of the class I aminoacyl-tRNA synthetase from Gardia lamblia forms a 16-residue alpha-helix. This helix replaces a beta-hairpin that is required by human TrpRS for normal activity and infers to play a similar role in all eukaryotic TrpRS |
716055 |
| 6.1.1.2 | evolution |
the Trypanosoma brucei genome contains separate cytosolic and mitochondrial isoforms of TrpRS that are both required and have diverged in their respective tRNA recognition domains |
716156 |
| 6.1.1.2 | malfunction |
a human mini K153Q TrpRS mutant cannot inhibit VEGF-stimulated HUVEC migration and cannot bind to the extracellular domain of VE-cadherin |
746452 |
| 6.1.1.2 | malfunction |
the angiostatic agent tryptophanyl-tRNA synthetase (TrpRS) is a dysregulated protein in oral squamous cell carcinoma (OSCC) based on a proteomics approach. TrpRS expression positively correlates with tumor stage, overall TNM stage, perineural invasion and tumor depth. TrpRS knockdown reduces cell viability and oral cancer cell migration and invasion |
745941 |
| 6.1.1.2 | malfunction |
the full-length-WRS-induced TNF-alpha and MIP-1alpha production is significantly inhibited when TLR4, MD2, and TLR2 (to lesser degree) are suppressed, full-length-WRS-induced neutrophil infiltration is almost ablated in the TLR4-/- and MD2-/- mice, and partially reduced in TLR2-/- mice. Although truncated WRS mutant lacking N47 can bring the two TLR4-MD2 complexes into proximity through homodimerization of the WRS catalytic domain, it may not be able to induce the functional dimerization of TLR4-MD2 to activate downstream signalling |
-, 745868 |
| 6.1.1.2 | malfunction |
the full-length-WRS-induced TNF-alpha and MIP-1alpha production is significantly inhibited when TLR4, MD2, and TLR2 (to lesser degree) are suppressed, human full-length-WRS-induced neutrophil infiltration is almost ablated in the TLR4-/- and MD2-/- mice, and partially reduced in TLR2-/- mice. Although truncated WRS mutant lacking N47 can bring the two TLR4-MD2 complexes into proximity through homodimerization of the WRS catalytic domain, it may not be able to induce the functional dimerization of TLR4-MD2 to activate downstream signalling |
745868 |
| 6.1.1.2 | more |
15N tryptophanyl-tRNA synthetase Urzyme structure analysis by heteronuclear single quantum coherence (HSQC) NMR spectroscopy supplemented by circular dichroism, thermal melting, and induced fluorescence of bound dye. TrpRS Urzyme is not a typical protein domain. Transition state stabilization and catalytic activity from molten globules, overview |
743913 |
| 6.1.1.2 | more |
both full-length TrpRS and mini-TrpRS splicing variants can be mobilized for exocytosis from endothelial cells, and the secreted TrpRS is cleaved by extracellular proteases to produce two additional N-terminally truncated fragments: T1-TrpRS (residues 71-471) and T2-TrpRS (residues 94-471). Extracellular treatment of TrpRS promotes cell invasion in oral cancer cells |
745941 |
| 6.1.1.2 | more |
both the ATP configuration and Mg2+ coordination in the human cytosolic (Hc)TrpRS preTS structure differ greatly from the BsTrpRS preTS structure. The effect of these differences is that catalysis occurs via a different transition state stabilization mechanism in HcTrpRS with a yet-to-be determined role for Mg2+ |
745352 |
