Publications

• Incorporation of amino acids into ribonucleic acid. I. The role of activating enzymes.

  ALLEN E.H., GLASSMAN E., SCHWEET R.S.

  J Biol Chem 235:1061-1067(1960) [PubMed] [EuropePMC]

  This publication is cited by 4 other entries.

• Lysyl-sRNA synthetase from Escherichia coli.

  Stern R., Mehler A.H.

  Biochem Z 342:400-409(1965) [PubMed] [EuropePMC]

• Structural switch of lysyl-tRNA synthetase between translation and transcription.

  Ofir-Birin Y., Fang P., Bennett S.P., Zhang H.M., Wang J., Rachmin I., Shapiro R., Song J., Dagan A., Pozo J., Kim S., Marshall A.G., Schimmel P., Yang X.L., Nechushtan H., Razin E., Guo M.

  Lysyl-tRNA synthetase (LysRS), a component of the translation apparatus, is released from the cytoplasmic multi-tRNA synthetase complex (MSC) to activate the transcription factor MITF in stimulated mast cells through undefined mechanisms. Here we show that Ser207 phosphorylation provokes a new con ... >> More

  Lysyl-tRNA synthetase (LysRS), a component of the translation apparatus, is released from the cytoplasmic multi-tRNA synthetase complex (MSC) to activate the transcription factor MITF in stimulated mast cells through undefined mechanisms. Here we show that Ser207 phosphorylation provokes a new conformer of LysRS that inactivates its translational function but activates its transcriptional function. The crystal structure of an MSC subcomplex established that LysRS is held in the MSC by binding to the N terminus of the scaffold protein p38/AIMP2. Phosphorylation-created steric clashes at the LysRS domain interface disrupt its binding grooves for p38/AIMP2, releasing LysRS and provoking its nuclear translocation. This alteration also exposes the C-terminal domain of LysRS to bind to MITF and triggers LysRS-directed production of the second messenger Ap(4)A that activates MITF. Thus our results establish that a single conformational change triggered by phosphorylation leads to multiple effects driving an exclusive switch of LysRS function from translation to transcription. << Less

  Mol. Cell 49:30-42(2013) [PubMed] [EuropePMC]

  This publication is cited by 4 other entries.

• Purification and properties of lysyl transfer ribonucleic acid synthetase from bakers' yeast.

  Chlumecka V., Von Tigerstrom M., D'Obrenan P., Smith C.J.

  J Biol Chem 244:5481-5488(1969) [PubMed] [EuropePMC]

• Characterization of a homogeneous arginyl- and lysyl-tRNA synthetase complex isolated from rat liver. Kinetic mechanism for lysyl-tRNA synthetase.

  Hilderman R.H., Zimmerman J.K., Dang C.V., Grothusen J.R.

  Bisubstrate kinetics and end product and dead end inhibition studies were performed on lysyl-tRNA synthetase isolated from rat liver. The kinetic patterns obtained are consistent with a sequential ordered mechanism of substrate addition, tRNA bound first, followed by lysine, and then by ATP. Pyrop ... >> More

  Bisubstrate kinetics and end product and dead end inhibition studies were performed on lysyl-tRNA synthetase isolated from rat liver. The kinetic patterns obtained are consistent with a sequential ordered mechanism of substrate addition, tRNA bound first, followed by lysine, and then by ATP. Pyrophosphate and AMP are released in a random fashion with aminoacylated tRNA the last product to dissociate from the enzyme. This is the first report of a kinetic mechanism for lysyl-tRNA synthetase. << Less

  J. Biol. Chem. 258:13592-13596(1983) [PubMed] [EuropePMC]

• Lysyl-tRNA synthetase interacts with EF1alpha, aspartyl-tRNA synthetase and p38 in vitro.

  Guzzo C.M., Yang D.C.H.

  The functions of evolved mammalian supramolecular assemblies and extensions of enzymes are not well understood. Human lysyl-tRNA synthetase (hKRS) only upon the removal of the amino-terminal extension (hKRSDelta60) bound to EF1alpha and was stimulated by EF1alphain vitro. HKRS and hKRSDelta60 were ... >> More

  The functions of evolved mammalian supramolecular assemblies and extensions of enzymes are not well understood. Human lysyl-tRNA synthetase (hKRS) only upon the removal of the amino-terminal extension (hKRSDelta60) bound to EF1alpha and was stimulated by EF1alphain vitro. HKRS and hKRSDelta60 were also differentially stimulated by aspartyl-tRNA synthetase (AspRS) from the multi-synthetase complex. The non-synthetase protein from the multi-synthetase complex p38 alone did not affect hKRS lysylation but inhibited the AspRS-mediated stimulation of hKRS. These results revealed the functional interactions of hKRS and shed new lights on the functional significance of the structural evolution of multienzyme complexes and appended extensions. << Less

  Biochem. Biophys. Res. Commun. 365:718-723(2008) [PubMed] [EuropePMC]

• Human lysyl-tRNA synthetase accepts nucleotide 73 variants and rescues Escherichia coli double-defective mutant.

  Shiba K., Stello T., Motegi H., Noda T., Musier-Forsyth K., Schimmel P.

  The nucleotide 73 (N73) "discriminator" base in the acceptor stem is a key element for efficient and specific aminoacylation of tRNAs and of microhelix substrates derived from tRNA acceptor stems. This nucleotide was possibly one of the first to be used for differentiating among groups of early RN ... >> More

  The nucleotide 73 (N73) "discriminator" base in the acceptor stem is a key element for efficient and specific aminoacylation of tRNAs and of microhelix substrates derived from tRNA acceptor stems. This nucleotide was possibly one of the first to be used for differentiating among groups of early RNA substrates by tRNA synthetases. In contrast to many other synthetases, we report here that the class II human lysyl-tRNA synthetase is relatively insensitive to the nature of N73. We cloned, sequenced, and expressed the enzyme, which is a close homologue of the class II yeast aspartyl-tRNA synthetase whose co-crystal structure (with tRNAAsp) is known. The latter enzyme has a strong requirement for G73, which interacts with 4 of the 14 residues within the "motif 2" loop of the enzyme. Even though eukaryotic lysine tRNAs also encode G73, the motif 2 loop sequence of lysyl-tRNA synthetase differs at multiple positions from that of the aspartate enzyme. Indeed, the recombinant human lysine enzyme shows little preference for G, and even charges human tRNA transcripts encoding the A73 found in E. coli lysine tRNAs. Moreover, while the lysine enzyme is the only one in E. coli to be encoded by two separate genes, a double mutant that disables both genes is complemented by a cDNA expressing the human protein. Thus, the sequence of the loop of motif 2 of human lysyl-tRNA synthetase specifies a structural variation that accommodates nucleotide degeneracy at position 73. This sequence might be used as a starting point for obtaining highly specific interactions with any given N73 by simple amino acid replacements. << Less

  J. Biol. Chem. 272:22809-22816(1997) [PubMed] [EuropePMC]

• Aminoacyl-tRNA synthesis.

  Ibba M., Soll D.

  Aminoacyl-tRNAs are substrates for translation and are pivotal in determining how the genetic code is interpreted as amino acids. The function of aminoacyl-tRNA synthesis is to precisely match amino acids with tRNAs containing the corresponding anticodon. This is primarily achieved by the direct a ... >> More

  Aminoacyl-tRNAs are substrates for translation and are pivotal in determining how the genetic code is interpreted as amino acids. The function of aminoacyl-tRNA synthesis is to precisely match amino acids with tRNAs containing the corresponding anticodon. This is primarily achieved by the direct attachment of an amino acid to the corresponding tRNA by an aminoacyl-tRNA synthetase, although intrinsic proofreading and extrinsic editing are also essential in several cases. Recent studies of aminoacyl-tRNA synthesis, mainly prompted by the advent of whole genome sequencing and the availability of a vast body of structural data, have led to an expanded and more detailed picture of how aminoacyl-tRNAs are synthesized. This article reviews current knowledge of the biochemical, structural, and evolutionary facets of aminoacyl-tRNA synthesis. << Less

  Annu Rev Biochem 69:617-650(2000) [PubMed] [EuropePMC]

  This publication is cited by 26 other entries.