6.1.1.1	evolution	analysis of evolutionary conservation of KMSKS motif in tyrosyl-tRNA synthetases, YRSs, two YRSs of Pyrococcus horikoshii and Leishmania major have an overall root mean squared deviation calculated as 3.2 A, although the primary sequences for ATP recognition motifs in Pyrococcus horikoshii and Leishmania major YRSs are identical (KMSKS). The KMSKS loop in YRSs is evolutionarily conserved and mediates inter-molecular interactions between YRS and ATP, Conformational landscape of KMSKS loops in YRSs, overview	-, 745655	
6.1.1.1	evolution	domain organization of TyrRS from eukaryotes and prokaryotes, overview	-, 745348	
6.1.1.1	evolution	mammalian TyrRS has evolved to be significantly less accurate than its bacterial counterpart. Different evolutionary constraints determine the accuracy of translation quality control in eukaryotes and bacteria. Functional comparisons of mammalian and bacterial tyrosyl-tRNA synthetase reveal key differences at residues responsible for amino acid recognition, highlighting differences in evolutionary constraints for translation quality control, overview	745300	
6.1.1.1	evolution	phylogenetic relationship of TyrRS sequences, schematic overview	715934	
6.1.1.1	evolution	the enzyme belongs to class I of aminoacyl-tRNA synthetases	-, 744822	
6.1.1.1	evolution	the enzyme belongs to the class I aminoacyl-tRNA synthetase family	-, 745576	
6.1.1.1	evolution	TyrRS belongs to the class I aminoacyl-tRNA synthetases (aaRSs), Evolutionary analysis of SerRS and TyrRS, overview	746475	
6.1.1.1	evolution	TyrRS is a member of class I aminoacyl-tRNA synthetases	744707	
6.1.1.1	malfunction	lysine acetylation can be a possible mechanism for modulating aminoacyl-tRNA synthetases enzyme activities, thus affecting translation. Of recombinantly expressed site-specifically acetylated TyrRS variants, TyrRS-85AcK and -235AcK show dramatic decreases in activity. Variant TyrRS-238AcK has no detectable activity, while variants TyrRS-144AcK and -355AcK have similar activities compared to the wild-type TyrRS. TyrRS-85AcK has a fivefold increase in the KM value for ATP, indicating its role in ATP binding. TyrRS-235AcK has slightly changed KM values for both ATP and tyrosine but a 200fold decrease in catalytic efficiency, suggesting its role in catalysis. K235 and K238 of TyrRS characterized in this study are the two lysine residues in the KMSKS motif. Kinetics for acetylated mutant variants, overview	744707	
6.1.1.1	malfunction	of six mutants tested, two are active towards D-Tyr; one of these has an inverted stereospecificity, with a large preference for D-Tyr, but its activity is low	746405	
6.1.1.1	malfunction	reduced amino acid specificity of mammalian tyrosyl-tRNA synthetase is associated with elevated mistranslation of Tyr codons. Mischarging of tRNATyr with noncognate Phe by tyrosyl-tRNA synthetase is responsible for mistranslation. Steady-state kinetic analyses of CHO cytoplasmic tyrosyl-tRNA synthetase reveals a 25fold lower specificity for Tyr over Phe as compared with previously characterized bacterial enzymes, consistent with the observed increase in translation error rates during tyrosine limitation	745300	
6.1.1.1	additional information	dissociating quaternary structures regulating novel functions of other tRNA synthetases	715585	
6.1.1.1	additional information	enzyme MtTyrRS contains the HIGH-like and KFGKS catalytic motifs that catalyze amino acid activation with ATP.The conformational mobility of MtTyrRS catalytic KFGKS loop is analyzed by 100-ns all-atoms molecular dynamics simulations of the free enzyme and its complexes with different substrates: tyrosine, ATP, and the tyrosyl-adenylate intermediate. In the closed state of the active site, the KFGKS loop, readily adopts different stable conformations depending on the type of bound substrate. The closed state of the loop is stabilized by dynamic formation of two antiparallel beta-sheets at flanking ends which hold the KFGKS fragment inside the active center. Molecular dynamics simulations, conformation of the MtTyrRS catalytic loop in substrate?bound states, detailed overview	-, 744822	
6.1.1.1	additional information	lysine acetylation could be a possible mechanism for modulating aminoacyl-tRNA synthetases enzyme activities, thus affecting translation	744707	
6.1.1.1	additional information	molecular dynamics modeling of substrates L- and D-Tyr into the active site of wild-type enzyme and mutants D81R and E36Q using the PDB ID 1J1U X-ray structure, superimposed based on their protein/tRNA environment, enzyme molecular dynamics simulation amd modeling, structure-function analysis, detailed overview	-, 745576	
6.1.1.1	additional information	residues, not conserved between bacteria and eukaryotes, Cys35, His48, Thr51, and Lys233 in bacterial TyrRS interact with ATP during transition state formation. Comparison the Geobacillus stearothermophilus, PDB ID 1tyd, and human, PDB ID 1q11, TyrRS active sites, overview. Hydrogen-bonding interactions between bacterial TyrRS residues Asp176 and Tyr34 and the substrate Tyr hydroxyl group help confer amino acid specificity to the enzyme	745300	
6.1.1.1	additional information	the LdTyrRS polypeptide chain consists of two pseudo-monomers, each consisting of two domains. Comparing the two independent chains in the asymmetric unit reveals that the two pseudo-monomers of LdTyrRS can bend with respect to each other essentially as rigid bodies. This flexibility might be useful in the positioning of tRNA for catalysis since both pseudo-monomers in the LdTyrRS chain are needed for charging tRNATyr. The LdTyrRS active site contains two critical pockets: the tyrosine binding pocket (YBP) where the tyrosyl group of inhibitor TyrSA is situated, and the adenine binding pocket (ABP) where the adenine moiety of TyrSA binds. Residues making hydrogen bonds with the TyrSA tyrosyl group in the tyrosine binding pocket (YBP) are Y36, Y163, Q167, D170 and Q185. Residues G38, A72 and F75 are responsible for the hydrophobic interactions between enzyme and tyrosine moiety in the YBP. An extra pocket (EP) appears to be present near the adenine binding. The extra pocket appears to be present near the adenine binding region of LdTyrRS, this pocket is absent in the two human homologous enzymes. Structure-based modelling, overview	744442	
6.1.1.1	additional information	the TyrRS stereospecificity is robust towards charge rearrangements near the ligand. Whereas most aminoacyl-tRNA synthetases (aaRSs) have a strong preference for their L-amino acid substrate, TyrRS has a detectable, natural activity for the D-tyrosine stereoisomer, only tenfold less than for L-Tyr; additional protection against D-Tyr is usually provided by another enzyme, D-aminoacyl-tRNA hydrolase. Enzyme molecular dynamics simulations using the crystal structure of Escherichia coli TyrRS bound to a tyrosyl adenylate analogue, PDB ID 1VBM	746405	
6.1.1.1	additional information	tyrosyl-tRNA synthetase structure comparisons, the KMSKS loop is very variable in conformation, intrinsic conformational heterogeneity in KMSKS loop that is independent of occupancy of active site. Differential centroid distance analyses between KMSKS motif and Rossmann fold domain reveal an intriguing bimodal distribution. The KMSKS loop is positioned at the intersection of Rossmann fold and the C-terminal region and plays a role in ATP binding and catalysis. KMSKS loop orientation and conformation can be independent of ATP binding, conformational flexibility of KMSKS loop, overview	-, 745655	
6.1.1.1	additional information	tyrosyl-tRNA synthetase structure comparisons, the KMSKS loop uís very variable in conformation, intrinsic conformational heterogeneity in KMSKS loop that is independent of occupancy of active site. Differential centroid distance analyses between KMSKS motif and Rossmann fold domain reveal an intriguing bimodal distribution. The KMSKS loop is positioned at the intersection of Rossmann fold and the C-terminal region and plays a role in ATP binding and catalysis. KMSKS loop orientation and conformation can be independent of ATP binding, conformational flexibility of KMSKS loop, overview	745655	
6.1.1.1	physiological function	aa-tRNA synthesis is a two-step reaction: activation of an amino acid with ATP to form aminoacyl adenylate, followed by transfer of the aminoacyl moiety to the 3' end of the tRNA. The error rate of this first step of translation is largely dependent on the specificity of the aaRS, that is selection of the correct amino acid and tRNA from the respective cellular pools of predominantly noncognate substrates. aaRSs select their cognate tRNAs by exploiting sequence-specific differences between various tRNAs during binding and aminoacylation. Translation of Tyr codons is highly prone to Phe isincorporation during amino acid limitation inCHOcells. CHO cell TyrRS is error-prone and readily aminoacylates tRNATyr with Phe, cf. EC 6.1.1.20. Steady-state kinetic analyses of CHO cytoplasmic tyrosyl-tRNA synthetase reveals a 25fold lower specificity for Tyr over Phe as compared with previously characterized bacterial enzymes, consistent with the observed increase in translation error rates during tyrosine limitation	745300	
6.1.1.1	physiological function	although native TyrRS has no known cytokine functions, natural proteolysis of secreted TyrRS releases TyrRSMini, which not only has the same aminoacylation activity as native TyrRS when occuring as a dimer, the monomer is inactive, but TyrRSMini also has strong activity for stimulating migration of polymorphonuclear leukocytes. The migration-stimulating activity is dependent on an ELR tripeptide motif, similar to that in CXC cytokines like IL-8, and also has the familiar bell-shaped concentration dependence seen for CXC cytokines. But TyrRSMini does not induce internalization of CXCR1/2. The TyrRSMini monomer is an agonist, while TyrRSMini dimer is an antagonist of induced PMN cell migration	715585	
6.1.1.1	physiological function	aminoacyl-tRNA synthetases (aaRSs) are housekeeping enzymes essential for protein synthesis. Apart from their parent aminoacylation activity, several aaRSs perform non-canonical functions in diverse biological processes. Leishmania tyrosyl-tRNA synthetase (LdTyrRS) performs aminoacylation and acts as a mimic of host CXC chemokine. Non-canonical function of Leishmania donovani tyrosyl-tRNA synthetase. The enzyme is essential. The released, extracellular LdTyrRS functions as a neutrophil chemoattractant. LdTyrRS specifically binds to host macrophages with its ELR (Glu-Leu-Arg) peptide motif. The ELR-CXCR2 receptor interaction mediates this binding. This interaction triggers enhanced secretion of the proinflammatory cytokines TNF-alpha and interleukin-6 by host macrophages. Possible immunomodulating role of LdTyrRS in Leishmania infection. Triggering of cytokine secretion by LdTyrRS, overview	-, 745348	
6.1.1.1	physiological function	aminoacyl-tRNA synthetases (aaRSs) for glycine, alanine, serine and tyrosine play important roles in fibroin synthesis	746475	
6.1.1.1	physiological function	CYT-18 also promotes self-splicing of group I intron RNAs by stabilizing the functional structure in the conserved core	705174	
6.1.1.1	physiological function	the flexibility and rapid dynamics of the wild-type aminoacyl-tRNA synthetase catalytic loop structure are crucial for formation of protein-substrate interactions and subsequently for overall enzyme functional activity, dynamic properties of the enzyme, overview	-, 744822	
6.1.1.1	physiological function	the human TyrRS can be split into two fragments with distinct signaling activities. The N-terminal fragment is an IL-8-like cytokine whereas the C-terminal fragment is more similar to endothelial monocyte-activating polypeptide II (EMAP II). Therapeutic effect of recombinant human tyrosyl-tRNA synthetase (rhTyrRS) against development of thrombocytopenia in cyclophosphamide (CTX) treated mice. Recombinant hTyrRS promotes migration and aggregation of megakaryocytes to the bone marrow niche. 1 is particularly important for the adhesion. The N-terminal fragment of the recombinant TyrRS acts as a chemoattractant molecule for M-07e cells, it stimulates adhesion of THP-1 cells to HUVECs and plays a role in the transendothelial migration of megakaryocytes and thrombocytopoiesis. All mice pretreated with rhTyrRS show a dose-dependent increase in megakaryocytes localized to the sinusoids. Recombinant human TyrRS enhances survival of cyclophosphamide (CTX) treated mice, that the bone marrow endothelial cells may enhance survival of megakaryocytes in the presence of rhTyrRS pretreatment	744846	
6.1.1.1	physiological function	tyrosyl-tRNA synthetase functions in group I intron splicing	714246	
6.1.1.1	physiological function	tyrosyl-tRNA synthetase is a potential kyotorphin synthetase (i.e. tyrosine-arginine ligase, EC 6.3.2.24) in mammals	745971