amino acyl trna synthetases


Summary: A subclass of enzymes that aminoacylate AMINO ACID-SPECIFIC TRANSFER RNA with their corresponding AMINO ACIDS.

Top Publications

  1. Fukunaga R, Yokoyama S. Structural insights into the second step of RNA-dependent cysteine biosynthesis in archaea: crystal structure of Sep-tRNA:Cys-tRNA synthase from Archaeoglobus fulgidus. J Mol Biol. 2007;370:128-41 pubmed publisher
    ..One of the three strictly conserved Cys residues (Cys39, Cys42, or Cys247), of one subunit may play a crucial role in the catalysis in the active site of the other subunit...
  2. Krzycki J. The direct genetic encoding of pyrrolysine. Curr Opin Microbiol. 2005;8:706-12 pubmed
    ..Thus, the recruitment of pyrrolysine into the genetic code involved evolution of the first non-canonical aminoacyl-tRNA synthetase and cognate tRNA to be described from nature...
  3. Rinehart J, Krett B, Rubio M, Alfonzo J, Soll D. Saccharomyces cerevisiae imports the cytosolic pathway for Gln-tRNA synthesis into the mitochondrion. Genes Dev. 2005;19:583-92 pubmed
    ..This tRNA import mechanism expands our knowledge of RNA trafficking in the eukaryotic cell. These findings change our view of the evolution of organellar protein synthesis. ..
  4. Sheppard K, Soll D. On the evolution of the tRNA-dependent amidotransferases, GatCAB and GatDE. J Mol Biol. 2008;377:831-44 pubmed publisher
    ..Archaeal GatCAB, on the other hand, has not favored a distinct tRNA(Asn), suggesting that tRNA(Asn) recognition is not a major barrier to the retention of asparaginyl-tRNA synthetase in many Archaea. ..
  5. O Donoghue P, Sethi A, Woese C, Luthey Schulten Z. The evolutionary history of Cys-tRNACys formation. Proc Natl Acad Sci U S A. 2005;102:19003-8 pubmed
    ..The model of SepCysS is used to suggest a sulfhydrylation reaction mechanism, which is predicted to occur at the interface of a SepCysS dimer. ..
  6. Zhang C, Perona J, Ryu K, Francklyn C, Hou Y. Distinct kinetic mechanisms of the two classes of Aminoacyl-tRNA synthetases. J Mol Biol. 2006;361:300-11 pubmed
    ..These results emphasize that the distinct mechanistic signatures of class I versus class II tRNA synthetases ensure rapid turnover of aminoacyl-tRNAs during protein synthesis. ..
  7. Skouloubris S, Ribas De Pouplana L, De Reuse H, Hendrickson T. A noncognate aminoacyl-tRNA synthetase that may resolve a missing link in protein evolution. Proc Natl Acad Sci U S A. 2003;100:11297-302 pubmed publisher
    ..We show that GluRS2's primary role is to generate Glu-tRNAGln, not Glu-tRNAGlu. Thus, GluRS2 appears to be a transient GluRS-like ancestor of GlnRS and can be defined as a GluGlnRS...
  8. Blight S, Larue R, Mahapatra A, Longstaff D, Chang E, Zhao G, et al. Direct charging of tRNA(CUA) with pyrrolysine in vitro and in vivo. Nature. 2004;431:333-5 pubmed
    ..This is the first example from nature of direct aminoacylation of a tRNA with a non-canonical amino acid and shows that the genetic code of E. coli can be expanded to include UAG-directed pyrrolysine incorporation into proteins. ..
  9. Ambrogelly A, Ahel I, Polycarpo C, Bunjun Srihari S, Krett B, Jacquin Becker C, et al. Methanocaldococcus jannaschii prolyl-tRNA synthetase charges tRNA(Pro) with cysteine. J Biol Chem. 2002;277:34749-54 pubmed publisher
    ..We discuss the implications of these results on the in vivo activity of the M. jannaschii ProRS and on the nature of the enzyme involved in the synthesis of Cys-tRNA(Cys) in M. jannaschii...

More Information


  1. Praetorius Ibba M, Hausmann C, Paras M, Rogers T, Ibba M. Functional association between three archaeal aminoacyl-tRNA synthetases. J Biol Chem. 2007;282:3680-7 pubmed
    ..These findings, together with earlier data, indicate the existence of a functional complex of three aminoacyl-tRNA synthetases in archaea in which LeuRS improves the catalytic efficiency of tRNA aminoacylation by both LysRS and ProRS...
  2. Schmitt E, Panvert M, Blanquet S, Mechulam Y. Structural basis for tRNA-dependent amidotransferase function. Structure. 2005;13:1421-33 pubmed publisher
    ..Comparison of GatD and L-asparaginase structures shows how the motion of a beta hairpin region containing a crucial catalytic threonine may control the overall reaction cycle of GatDE...
  3. Deniziak M, Sauter C, Becker H, Paulus C, Gieg R, Kern D. Deinococcus glutaminyl-tRNA synthetase is a chimer between proteins from an ancient and the modern pathways of aminoacyl-tRNA formation. Nucleic Acids Res. 2007;35:1421-31 pubmed publisher
    ..However, the presence of Yqey in free state in organisms lacking GlnRS, suggests that this domain may exert additional cellular functions...
  4. Ruan B, Soll D. The bacterial YbaK protein is a Cys-tRNAPro and Cys-tRNA Cys deacylase. J Biol Chem. 2005;280:25887-91 pubmed
    ..These data suggest that YbaK-mediated hydrolysis of aminoacyl-tRNA can influence cell growth...
  5. Ryckelynck M, Giege R, Frugier M. tRNAs and tRNA mimics as cornerstones of aminoacyl-tRNA synthetase regulations. Biochimie. 2005;87:835-45 pubmed
    ..Such mechanisms are diverse and intervene in transcription, splicing and translation. Altogether, the review highlights the many manners architectural features of tRNA were selected by evolution to control biological key processes. ..
  6. Sauerwald A, Zhu W, Major T, Roy H, Palioura S, Jahn D, et al. RNA-dependent cysteine biosynthesis in archaea. Science. 2005;307:1969-72 pubmed publisher
  7. Kamtekar S, Hohn M, Park H, Schnitzbauer M, Sauerwald A, S ll D, et al. Toward understanding phosphoseryl-tRNACys formation: the crystal structure of Methanococcus maripaludis phosphoseryl-tRNA synthetase. Proc Natl Acad Sci U S A. 2007;104:2620-5 pubmed publisher
    ..Using a complex with tungstate as a marker for the position of the phosphate moiety of Sep, we suggest that SepRS and PheRS bind their respective amino acid substrates in dissimilar orientations by using different residues...
  8. Park S, Ewalt K, Kim S. Functional expansion of aminoacyl-tRNA synthetases and their interacting factors: new perspectives on housekeepers. Trends Biochem Sci. 2005;30:569-74 pubmed
    ..Evaluation of the functional roles of individual ARSs and AIMPs might help to elucidate why these proteins as a whole contribute such varied functions and interactions in complex systems. ..
  9. Roy H, Becker H, Reinbolt J, Kern D. When contemporary aminoacyl-tRNA synthetases invent their cognate amino acid metabolism. Proc Natl Acad Sci U S A. 2003;100:9837-42 pubmed
    ..This study provides evidence that a contemporary aminoacyl-tRNA synthetase can be recruited to sustain amino acid metabolism. ..
  10. Hohsaka T, Sisido M. Incorporation of non-natural amino acids into proteins. Curr Opin Chem Biol. 2002;6:809-15 pubmed
    ..The combination of these novel techniques has opened the possibility of synthesising non-natural mutant proteins in living cells. ..
  11. Salazar J, Ambrogelly A, Crain P, McCloskey J, Soll D. A truncated aminoacyl-tRNA synthetase modifies RNA. Proc Natl Acad Sci U S A. 2004;101:7536-41 pubmed
    ..Thus, this aminoacyl-tRNA synthetase fragment contributes to standard nucleotide modification of tRNA. ..
  12. Polycarpo C, Ambrogelly A, Bérubé A, Winbush S, McCloskey J, Crain P, et al. An aminoacyl-tRNA synthetase that specifically activates pyrrolysine. Proc Natl Acad Sci U S A. 2004;101:12450-4 pubmed
    ..This would ensure efficient translation of the in-frame UAG codon in case of pyrrolysine deficiency and safeguard the biosynthesis of the proteins whose genes contain this special codon...
  13. Hausmann C, Ibba M. Aminoacyl-tRNA synthetase complexes: molecular multitasking revealed. FEMS Microbiol Rev. 2008;32:705-21 pubmed publisher
  14. Vasil eva I, Moor N. Interaction of aminoacyl-tRNA synthetases with tRNA: general principles and distinguishing characteristics of the high-molecular-weight substrate recognition. Biochemistry (Mosc). 2007;72:247-63 pubmed
    ..Diversity and identity of biochemical functions of the recognition elements make substantial contribution to the specificity of such interactions. ..
  15. Chin J, Cropp T, Chu S, Meggers E, Schultz P. Progress toward an expanded eukaryotic genetic code. Chem Biol. 2003;10:511-9 pubmed
    ..This method will facilitate the isolation of a range of aminoacyl-tRNA synthetase (aaRS)/tRNA(CUA) activities from large libraries of mutant synthetases. ..
  16. Giege R. The early history of tRNA recognition by aminoacyl-tRNA synthetases. J Biosci. 2006;31:477-88 pubmed
  17. Herring S, Ambrogelly A, Polycarpo C, Soll D. Recognition of pyrrolysine tRNA by the Desulfitobacterium hafniense pyrrolysyl-tRNA synthetase. Nucleic Acids Res. 2007;35:1270-8 pubmed
    ..A58 and position 57 is conserved as a purine, but the canonical T- to D-loop contact between positions 18 and 56 was not present. Unlike most tRNAs, the tRNA(Pyl) anticodon was shown not to be important for recognition by bacterial PylRS...
  18. Yanagisawa T, Ishii R, Fukunaga R, Kobayashi T, Sakamoto K, Yokoyama S. Crystallographic studies on multiple conformational states of active-site loops in pyrrolysyl-tRNA synthetase. J Mol Biol. 2008;378:634-52 pubmed publisher
    ..In addition, a docking model of PylRS with tRNA was constructed based on the aspartyl-tRNA synthetase/tRNA structure, and was confirmed by a mutational analysis...
  19. Deniziak M, Sauter C, Becker H, Giege R, Kern D. Crystallization and preliminary X-ray characterization of the atypical glutaminyl-tRNA synthetase from Deinococcus radiodurans. Acta Crystallogr D Biol Crystallogr. 2004;60:2361-3 pubmed
    ..Orthorhombic crystals were obtained that belong to space group P2(1)2(1)2(1) and diffract to 2.3 A resolution. The crystal structure was solved by molecular replacement using the structure of E. coli GlnRS as a search model. ..
  20. Bullock T, Uter N, Nissan T, Perona J. Amino acid discrimination by a class I aminoacyl-tRNA synthetase specified by negative determinants. J Mol Biol. 2003;328:395-408 pubmed
    ..The poorly differentiated cognate amino acid-binding site in GlnRS may be a consequence of the late emergence of this enzyme from the eukaryotic lineage of glutamyl-tRNA synthetases. ..
  21. Neumann H, Peak Chew S, Chin J. Genetically encoding N(epsilon)-acetyllysine in recombinant proteins. Nat Chem Biol. 2008;4:232-4 pubmed publisher
    ..This strategy should find wide applications in defining the cellular role of this modification...
  22. Francklyn C, Perona J, Puetz J, Hou Y. Aminoacyl-tRNA synthetases: versatile players in the changing theater of translation. RNA. 2002;8:1363-72 pubmed
  23. Wong F, Beuning P, Nagan M, Shiba K, Musier Forsyth K. Functional role of the prokaryotic proline-tRNA synthetase insertion domain in amino acid editing. Biochemistry. 2002;41:7108-15 pubmed
    ..Our biochemical data and modeling studies suggest that the prokaryotic INS plays a critical role in editing and that this activity resides in a domain that is functionally and structurally distinct from the aminoacylation active site. ..
  24. Praetorius Ibba M, Rogers T, Samson R, Kelman Z, Ibba M. Association between Archaeal prolyl- and leucyl-tRNA synthetases enhances tRNA(Pro) aminoacylation. J Biol Chem. 2005;280:26099-104 pubmed publisher
    ..These findings indicate that ProRS and LeuRS associate in M. thermautotrophicus and suggest that this interaction contributes to translational fidelity by enhancing tRNA aminoacylation by ProRS...
  25. Polycarpo C, Herring S, Bérubé A, Wood J, Soll D, Ambrogelly A. Pyrrolysine analogues as substrates for pyrrolysyl-tRNA synthetase. FEBS Lett. 2006;580:6695-700 pubmed
    ..Furthermore, the formation of active beta-galactosidase shows that a specialized mRNA motif is not essential for stop-codon recoding, unlike for selenocysteine incorporation. ..
  26. Fukunaga J, Yokogawa T, Ohno S, Nishikawa K. Misacylation of yeast amber suppressor tRNA(Tyr) by E. coli lysyl-tRNA synthetase and its effective repression by genetic engineering of the tRNA sequence. J Biochem. 2006;139:689-96 pubmed
    ..This "optimized" tRNA together with our mutant TyrRS should serve as an efficient and faithful tool for site-specific incorporation of unnatural amino acids into proteins in a protein-synthesizing system in vitro or in vivo. ..
  27. Wong F, Beuning P, Silvers C, Musier Forsyth K. An isolated class II aminoacyl-tRNA synthetase insertion domain is functional in amino acid editing. J Biol Chem. 2003;278:52857-64 pubmed
    ..Thus, we demonstrate for the first time that an independently folded class II synthetase editing domain and a previously identified homolog can catalyze a hydrolytic editing reaction. ..
  28. Han J, Kim J, Kim S. Molecular network and functional implications of macromolecular tRNA synthetase complex. Biochem Biophys Res Commun. 2003;303:985-93 pubmed
    ..In this review, the molecular mechanism for the assembly and functional implications of the multi-ARS complex will be discussed. ..
  29. Jia J, Arif A, Ray P, Fox P. WHEP domains direct noncanonical function of glutamyl-Prolyl tRNA synthetase in translational control of gene expression. Mol Cell. 2008;29:679-90 pubmed publisher
    ..Our results establish the essentiality of WHEP domains in the noncanonical function of EPRS in regulating inflammatory gene expression. ..
  30. Perona J, Hou Y. Indirect readout of tRNA for aminoacylation. Biochemistry. 2007;46:10419-32 pubmed
    ..The examples of indirect readout in tRNA synthetase complexes extend the concept beyond its traditional application to DNA duplexes and serve as models for the operation of this mechanism in more complex systems such as the ribosome. ..
  31. Hauenstein S, Perona J. Redundant synthesis of cysteinyl-tRNACys in Methanosarcina mazei. J Biol Chem. 2008;283:22007-17 pubmed publisher
    ..Together, these data suggest that both metabolic routes and all three tRNA(Cys) species in M. mazei play important roles in the cellular physiology of the organism...
  32. Chong Y, Yang X, Schimmel P. Natural homolog of tRNA synthetase editing domain rescues conditional lethality caused by mistranslation. J Biol Chem. 2008;283:30073-8 pubmed publisher
    ..The results support the idea that the unique widespread distribution of AlaXp arises from the singular difficulties, for translation, poised by alanine...
  33. Sokabe M, Okada A, Yao M, Nakashima T, Tanaka I. Molecular basis of alanine discrimination in editing site. Proc Natl Acad Sci U S A. 2005;102:11669-74 pubmed publisher
    ..These observations strongly suggested conservation of the chemical discrimination among trans- and cis-editing of tRNA(Ala)...
  34. Kim J, Kang Y, Lee J, Kim H, Ahn Y, Park H, et al. p38 is essential for the assembly and stability of macromolecular tRNA synthetase complex: implications for its physiological significance. Proc Natl Acad Sci U S A. 2002;99:7912-6 pubmed
    ..The mutant mice showed lethality within 2 days of birth. Thus, this work provides the first evidence, to our knowledge, that p38 is essential for the structural integrity of the multi-tRNA synthetase complex and mouse viability. ..
  35. Wolfe C, Warrington J, Treadwell L, Norcum M. A three-dimensional working model of the multienzyme complex of aminoacyl-tRNA synthetases based on electron microscopic placements of tRNA and proteins. J Biol Chem. 2005;280:38870-8 pubmed
    ..This is the first conceptualization of how the protein constituents and tRNA substrates are arrayed within the structural confines of this multiprotein assembly. ..
  36. Rodin S, Rodin A. Partitioning of aminoacyl-tRNA synthetases in two classes could have been encoded in a strand-symmetric RNA world. DNA Cell Biol. 2006;25:617-26 pubmed
    ..The principle of evolutionary continuity suggests that their protein successors also arose on complementary strands. Our analyses support this hypothesis. ..
  37. Wolfson A, Knight R. Occurrence of the aminoacyl-tRNA synthetases in high-molecular weight complexes correlates with the size of substrate amino acids. FEBS Lett. 2005;579:3467-72 pubmed
    ..The significance of this association is discussed in terms of the structural organization of translation in the living cell. ..
  38. Akochy P, Bernard D, Roy P, Lapointe J. Direct glutaminyl-tRNA biosynthesis and indirect asparaginyl-tRNA biosynthesis in Pseudomonas aeruginosa PAO1. J Bacteriol. 2004;186:767-76 pubmed
    ..Such novel antibiotics could be active against other multidrug-resistant gram-negative pathogens such as Burkholderia and Neisseria as well as all pathogenic gram-positive bacteria. ..
  39. An S, Musier Forsyth K. Cys-tRNA(Pro) editing by Haemophilus influenzae YbaK via a novel synthetase.YbaK.tRNA ternary complex. J Biol Chem. 2005;280:34465-72 pubmed publisher
    ..These results suggest that the specificity of trans-editing by YbaK is ensured through formation of a novel ProRS.YbaK.tRNA complex...
  40. Mucha P. Aminoacyl-tRNA synthetases and aminoacylation of tRNA in the nucleus. Acta Biochim Pol. 2002;49:1-10 pubmed
    ..Nuclear coupling of both these processes show us how exciting and surprising may be the world of the living cell. ..
  41. Ambrogelly A, Gundllapalli S, Herring S, Polycarpo C, Frauer C, Soll D. Pyrrolysine is not hardwired for cotranslational insertion at UAG codons. Proc Natl Acad Sci U S A. 2007;104:3141-6 pubmed
    ..coli. These data suggest that tRNA(Pyl) variants may decode numerous codons and that tRNA(Pyl):PylRS is a fine orthogonal tRNA:synthetase pair that facilitated the late addition of Pyl to the genetic code...
  42. Herring S, Ambrogelly A, Gundllapalli S, O Donoghue P, Polycarpo C, Soll D. The amino-terminal domain of pyrrolysyl-tRNA synthetase is dispensable in vitro but required for in vivo activity. FEBS Lett. 2007;581:3197-203 pubmed
    ..We also show that the amino-terminal extension present in archaeal PylRSs is dispensable for in vitro activity, but required for PylRS function in vivo...
  43. An S, Musier Forsyth K. Trans-editing of Cys-tRNAPro by Haemophilus influenzae YbaK protein. J Biol Chem. 2004;279:42359-62 pubmed
    ..This work also suggests a novel mechanism of editing wherein a third sieve is used to clear Cys-tRNAPro in at least some organisms. ..
  44. Salazar J, Ahel I, Orellana O, Tumbula Hansen D, Krieger R, Daniels L, et al. Coevolution of an aminoacyl-tRNA synthetase with its tRNA substrates. Proc Natl Acad Sci U S A. 2003;100:13863-8 pubmed publisher
    ..The coexistence of the two GluRS enzymes in one organism may lay the groundwork for the acquisition of the canonical glutaminyl-tRNA synthetase by lateral gene transfer from eukaryotes...
  45. O Donoghue P, Luthey Schulten Z. On the evolution of structure in aminoacyl-tRNA synthetases. Microbiol Mol Biol Rev. 2003;67:550-73 pubmed
    ..We also discuss the effect of functional specificity on protein shape over the complex evolutionary course of the tRNA synthetases. ..
  46. Sherlin L, Perona J. tRNA-dependent active site assembly in a class I aminoacyl-tRNA synthetase. Structure. 2003;11:591-603 pubmed
  47. Kavran J, Gundllapalli S, O Donoghue P, Englert M, S ll D, Steitz T. Structure of pyrrolysyl-tRNA synthetase, an archaeal enzyme for genetic code innovation. Proc Natl Acad Sci U S A. 2007;104:11268-73 pubmed publisher
    ..The PylRS structure provides an excellent framework for designing new aaRSs with altered amino acid specificity...
  48. Sampath P, Mazumder B, Seshadri V, Gerber C, Chavatte L, Kinter M, et al. Noncanonical function of glutamyl-prolyl-tRNA synthetase: gene-specific silencing of translation. Cell. 2004;119:195-208 pubmed
  49. Schimmel P, Ewalt K. Translation silenced by fused pair of tRNA synthetases. Cell. 2004;119:147-8 pubmed
    ..GluProRS is released from a multisynthetase translation complex in response to gamma-interferon and forms a four-protein GAIT complex that silences translation of ceruloplasmin (Cp), a protein linked to the inflammatory response. ..
  50. Sareen D, Steffek M, Newton G, Fahey R. ATP-dependent L-cysteine:1D-myo-inosityl 2-amino-2-deoxy-alpha-D-glucopyranoside ligase, mycothiol biosynthesis enzyme MshC, is related to class I cysteinyl-tRNA synthetases. Biochemistry. 2002;41:6885-90 pubmed
    ..The cysS2 gene was thought to encode a second cysteinyl-tRNA synthetase in addition to cysS but the present results indicate that cysS2 is actually the mshC gene encoding ATP-dependent Cys:GlcN-Ins ligase...
  51. Stathopoulos C, Li T, Longman R, Vothknecht U, Becker H, Ibba M, et al. One polypeptide with two aminoacyl-tRNA synthetase activities. Science. 2000;287:479-82 pubmed
    ..The ability of one enzyme to provide two aminoacyl-tRNAs for protein synthesis raises questions about concepts of substrate specificity in protein synthesis and may provide insights into the evolutionary origins of this process...
  52. Wakasugi K, Quinn C, Tao N, Schimmel P. Genetic code in evolution: switching species-specific aminoacylation with a peptide transplant. EMBO J. 1998;17:297-305 pubmed
    ..Thus, functionally important co-adaptations of a synthetase to its tRNA act as small modular units that can be moved across taxonomic domains and thereby preserve the universality of the code. ..
  53. Sankaranarayanan R, Dock Bregeon A, Romby P, Caillet J, Springer M, Rees B, et al. The structure of threonyl-tRNA synthetase-tRNA(Thr) complex enlightens its repressor activity and reveals an essential zinc ion in the active site. Cell. 1999;97:371-81 pubmed
    ..A zinc ion found in the active site is implicated in amino acid recognition/discrimination...