alanine trna ligase


Summary: An enzyme that activates alanine with its specific transfer RNA. EC

Top Publications

  1. Beebe K, Ribas De Pouplana L, Schimmel P. Elucidation of tRNA-dependent editing by a class II tRNA synthetase and significance for cell viability. EMBO J. 2003;22:668-75 pubmed
    ..Thus, tRNA-dependent editing by AlaRS may have been critical for making the genetic code sufficiently accurate to generate the tree of life. ..
  2. Swairjo M, Schimmel P. Breaking sieve for steric exclusion of a noncognate amino acid from active site of a tRNA synthetase. Proc Natl Acad Sci U S A. 2005;102:988-93 pubmed publisher
    ..Significantly, in the Mg2+-ATP complex, Asn-194 coordinates a Mg2+-alpha-phosphate bridge. Thus, the sieve for Ser exclusion is broken because of selective pressure to retain Asn-194 for Mg2+-ATP and Ala binding...
  3. Chang K, Lin G, Men L, Wang C. Redundancy of non-AUG initiators. A clever mechanism to enhance the efficiency of translation in yeast. J Biol Chem. 2006;281:7775-83 pubmed
    ..Cumulatively, the results suggest that this feature of redundancy of non-AUG initiators in a single mRNA per se may represent a novel paradigm for improving the efficiency of a poor or otherwise nonproductive initiation event. ..
  4. Guo M, Chong Y, Beebe K, Shapiro R, Yang X, Schimmel P. The C-Ala domain brings together editing and aminoacylation functions on one tRNA. Science. 2009;325:744-7 pubmed publisher
    ..In addition, C-Ala may have played an essential role in the evolution of AlaRSs by coupling aminoacylation to editing to prevent mistranslation. ..
  5. Davis M, Buechter D, Schimmel P. Functional dissection of a predicted class-defining motif in a class II tRNA synthetase of unknown structure. Biochemistry. 1994;33:9904-11 pubmed
    ..The results suggest that similar analyses will be generally useful in testing models for active site regions of other class II aminoacyl-tRNA synthetases of unknown structure. ..
  6. Shi J, Musier Forsyth K, Schimmel P. Region of a conserved sequence motif in a class II tRNA synthetase needed for transfer of an activated amino acid to an RNA substrate. Biochemistry. 1994;33:5312-8 pubmed
    ..Because D235 in alanine tRNA synthetase is at the beginning of one of the conserved motifs that define class II tRNA synthetases, this region of the structure may in general be important for the transfer step. ..
  7. Lee J, Beebe K, Nangle L, Jang J, Longo Guess C, Cook S, et al. Editing-defective tRNA synthetase causes protein misfolding and neurodegeneration. Nature. 2006;443:50-5 pubmed
    ..These findings demonstrate that disruption of translational fidelity in terminally differentiated neurons leads to the accumulation of misfolded proteins and cell death, and provide a novel mechanism underlying neurodegeneration. ..
  8. Huang H, Tang H, Chao H, Yeh L, Wang C. An unusual pattern of protein expression and localization of yeast alanyl-tRNA synthetase isoforms. Mol Microbiol. 2006;60:189-98 pubmed
    ..Thus, the sequence upstream of the first in-frame AUG initiator not only carries an unusual initiation site, but also contributes to a novel pattern of protein expression and localization. ..
  9. Beebe K, Mock M, Merriman E, Schimmel P. Distinct domains of tRNA synthetase recognize the same base pair. Nature. 2008;451:90-3 pubmed publisher
    ..These also recognize mischarged tRNA(Ala). Thus, through evolution, three different complexes with the same tRNA can guard against mistaking glycine or serine for alanine...

More Information


  1. Barends S, Wower J, Kraal B. Kinetic parameters for tmRNA binding to alanyl-tRNA synthetase and elongation factor Tu from Escherichia coli. Biochemistry. 2000;39:2652-8 pubmed
    ..These observations can be interpreted to suggest that additional factors facilitate tmRNA binding to ribosomes. ..
  2. Yamasaki Y, Yamada H, Nozaki T, Akaogi J, Nichols C, Lyons R, et al. Unusually high frequency of autoantibodies to PL-7 associated with milder muscle disease in Japanese patients with polymyositis/dermatomyositis. Arthritis Rheum. 2006;54:2004-9 pubmed
    ..Although anti-PL-7, similar to anti-Jo-1, is associated with PM/DM with ILD, muscle involvement in the patients with anti-PL-7 appeared to be milder than that in the anti-Jo-1 subset. ..
  3. Shen L, Basilion J, Stanton V. Single-nucleotide polymorphisms can cause different structural folds of mRNA. Proc Natl Acad Sci U S A. 1999;96:7871-6 pubmed
    ..These results demonstrate the contribution of common genetic variation to structural diversity of mRNA and suggest a broader role than previously thought for the effects of SNPs on mRNA structure and, ultimately, biological function. ..
  4. Pleiss J, Derrick M, Uhlenbeck O. T7 RNA polymerase produces 5' end heterogeneity during in vitro transcription from certain templates. RNA. 1998;4:1313-7 pubmed
    ..The presence of this 5' end heterogeneity in combination with the 3' end heterogeneity common to T7 transcriptions results in a mixture of RNA molecules even after rigorous size purification. ..
  5. Wang Y, Sekiguchi T, Noguchi E, Nishimoto T. A hamster temperature-sensitive alanyl-tRNA synthetase mutant causes degradation of cell-cycle related proteins and apoptosis. J Biochem. 2004;135:7-16 pubmed
    ..5 degrees C. However, the defects of these mutants released EMAPII, an inducer of apoptosis at 39.5 degrees C. No release of EMAPII occurred in ts ET12 cells at 39.5 degrees C, consistent with the delay of apoptosis in these cells. ..
  6. Miller W, Schimmel P. A retroviral-like metal binding motif in an aminoacyl-tRNA synthetase is important for tRNA recognition. Proc Natl Acad Sci U S A. 1992;89:2032-5 pubmed
    ..These and additional experiments collectively suggest a role for the retroviral-like metal binding motif in RNA recognition and, further, raise the possibility that the protein-bound metal itself participates in an RNA interaction. ..
  7. Mireau H, Cosset A, Marechal Drouard L, Fox T, Small I, Dietrich A. Expression of Arabidopsis thaliana mitochondrial alanyl-tRNA synthetase is not sufficient to trigger mitochondrial import of tRNAAla in yeast. J Biol Chem. 2000;275:13291-6 pubmed
    ..thaliana tRNA(Ala) nor of the endogenous cytosolic tRNA(Ala) isoacceptors. We conclude that at least one other factor besides the mitochondrial AlaRS precursor must be involved in mitochondrial import of tRNA(Ala) in plants. ..
  8. Hausmann C, Praetorius Ibba M, Ibba M. An aminoacyl-tRNA synthetase:elongation factor complex for substrate channeling in archaeal translation. Nucleic Acids Res. 2007;35:6094-102 pubmed
  9. Sokabe M, Ose T, Nakamura A, Tokunaga K, Nureki O, Yao M, et al. The structure of alanyl-tRNA synthetase with editing domain. Proc Natl Acad Sci U S A. 2009;106:11028-33 pubmed publisher
    ..As Asn-194 in eubacterial AlaRS important for Ser misactivation is replaced by Thr-213 in archaeal AlaRS, a different Ser accommodation mechanism is proposed...
  10. Hou Y, Schimmel P. Modeling with in vitro kinetic parameters for the elaboration of transfer RNA identity in vivo. Biochemistry. 1989;28:4942-7 pubmed
    ..The results delineate some of the kinetic boundaries for the design and accommodation of tRNA sequence variations in the elaboration of identity in vivo. ..
  11. Carneiro V, Dietrich A, Marechal Drouard L, Cosset A, Pelletier G, Small I. Characterization of some major identity elements in plant alanine and phenylalanine transfer RNAs. Plant Mol Biol. 1994;26:1843-53 pubmed
  12. Maas S, Kim Y, Rich A. Genomic clustering of tRNA-specific adenosine deaminase ADAT1 and two tRNA synthetases. Mamm Genome. 2001;12:387-93 pubmed
    ..The clustering of three tRNA specific genes, of which two are specific for tRNA(Ala), may indicate their evolutionary relatedness or common factors involved in regulating their expression. ..
  13. Swairjo M, Otero F, Yang X, Lovato M, Skene R, McRee D, et al. Alanyl-tRNA synthetase crystal structure and design for acceptor-stem recognition. Mol Cell. 2004;13:829-41 pubmed
    ..It also suggests conformational flexibility within the C domain, which might allow for the positional variation of the key G:U base pair seen in some tRNA(Ala)s...
  14. Fischer A, Beuning P, Musier Forsyth K. Identification of discriminator base atomic groups that modulate the alanine aminoacylation reaction. J Biol Chem. 1999;274:37093-6 pubmed
    ..Taken together, these new results are consistent with the involvement of major groove atomic groups of the discriminator base in the formation of the transition state for the amino acid transfer step. ..
  15. Guiliani N, Bengrine A, Borne F, Chippaux M, Bonnefoy V. Alanyl-tRNA synthetase gene of the extreme acidophilic chemolithoautotrophic Thiobacillus ferrooxidans is highly homologous to alaS genes from all living kingdoms but cannot be transcribed from its promoter in Escherichia coli. Microbiology. 1997;143 ( Pt 7):2179-87 pubmed
    ..Two regions, one of which corresponds to the catalytic core, are particularly well-conserved at the nucleotide sequence level, a possible indication of strong constraints during evolution on these parts of the genes...
  16. Peragallo J, Keller S, van der Knaap M, Soares B, Shankar S. Retinopathy and optic atrophy: Expanding the phenotypic spectrum of pathogenic variants in the AARS2 gene. Ophthalmic Genet. 2018;39:99-102 pubmed publisher
    ..R722Q)], found to be in trans on parental testing. Missense variants in the AARS2 gene are the likely cause of the retinopathy and optic atrophy in this patient. This finding expands the phenotypic spectrum of the AARS2 gene. ..
  17. Roy H, Ibba M. Molecular biology: sticky end in protein synthesis. Nature. 2006;443:41-2 pubmed
  18. Stepanov V, Nyborg J. tmRNA from Thermus thermophilus. Interaction with alanyl-tRNA synthetase and elongation factor Tu. Eur J Biochem. 2003;270:463-75 pubmed
    ..Studies on EF-Tu protection of Ala approximately tmRNA against alkaline hydrolysis revealed the existence of at least two different binding sites for EF-Tu on charged tmRNA. The possible nature of these binding sites is discussed. ..
  19. Jovanovic M, Lilic M, Janjusevic R, Jovanovic G, Savic D, Milija J. tRNA synthetase mutants of Escherichia coli K-12 are resistant to the gyrase inhibitor novobiocin. J Bacteriol. 1999;181:2979-83 pubmed
    ..Under conditions of stringent response induction, either by the presence of tRNA synthetase mutations or by constitutive production of RelA protein, inactivation of the cls gene diminishes resistance to novobiocin but not to mecillinam. ..
  20. Liu H, Kessler J, Peterson R, Musier Forsyth K. Evidence for class-specific discrimination of a semiconserved base pair by tRNA synthetases. Biochemistry. 1995;34:9795-800 pubmed
    ..C72 base pair proximal to the amino acid attachment site. ..
  21. Herlihy W, Royal N, Biemann K, Putney S, Schimmel P. Mass spectra of partial protein hydrolysates as a multiple phase check for long polypeptides deduced from DNA sequences: NH2-terminal segment of alanine tRNA synthetase. Proc Natl Acad Sci U S A. 1980;77:6531-5 pubmed
    ..This paper reports the sequence of the first 165 amino acids from the NH2 terminus. ..
  22. Guo M, Shapiro R, Schimmel P, Yang X. Introduction of a leucine half-zipper engenders multiple high-quality crystals of a recalcitrant tRNA synthetase. Acta Crystallogr D Biol Crystallogr. 2010;66:243-50 pubmed publisher
    ..The authors propose that the method can be unified with surface-entropy reduction and can be broadly used for protein-surface optimization in crystallization. ..
  23. Francklyn C, Schimmel P. Aminoacylation of RNA minihelices with alanine. Nature. 1989;337:478-81 pubmed
    ..Alanine incorporation requires a single G.U base pair, and occurs in helices that otherwise differ significantly in sequence. Aminoacylation can be achieved with only seven base pairs in the helix. ..
  24. Naganuma M, Sekine S, Fukunaga R, Yokoyama S. Unique protein architecture of alanyl-tRNA synthetase for aminoacylation, editing, and dimerization. Proc Natl Acad Sci U S A. 2009;106:8489-94 pubmed publisher
    ..The helical subdomain mediates dimerization by forming a helix-loop-helix zipper. The globular subdomain, which is important for the aminoacylation and editing activities, has a positively-charged face suitable for tRNA binding. ..
  25. Chihade J, Brown J, Schimmel P, Ribas de Pouplana L. Origin of mitochondria in relation to evolutionary history of eukaryotic alanyl-tRNA synthetase. Proc Natl Acad Sci U S A. 2000;97:12153-7 pubmed
    ..Moreover, the data raise the possibility that diplomonads are primary amitochondriates that radiated from the eukaryotic lineage before mitochondria became fully integrated as a cellular organelle. ..
  26. Klenk H, Meier T, Durovic P, Schwass V, Lottspeich F, Dennis P, et al. RNA polymerase of Aquifex pyrophilus: implications for the evolution of the bacterial rpoBC operon and extremely thermophilic bacteria. J Mol Evol. 1999;48:528-41 pubmed
    ..This raised doubts not only about whether the original Bacteria were indeed like the hyperthermophiles, but also concerning the value of single-gene phylogenies for hypotheses about the evolution of organisms...
  27. Beuning P, Nagan M, Cramer C, Musier Forsyth K, Gelpi J, Bashford D. Efficient aminoacylation of the tRNA(Ala) acceptor stem: dependence on the 2:71 base pair. RNA. 2002;8:659-70 pubmed
    ..This analysis revealed a positive correlation between major groove negative electrostatic potential in the vicinity of the 3:70 base pair and measured aminoacylation efficiency. ..
  28. Ribas de Pouplana L, Buechter D, Sardesai N, Schimmel P. Functional analysis of peptide motif for RNA microhelix binding suggests new family of RNA-binding domains. EMBO J. 1998;17:5449-57 pubmed
  29. Beebe K, Merriman E, Schimmel P. Structure-specific tRNA determinants for editing a mischarged amino acid. J Biol Chem. 2003;278:45056-61 pubmed
    ..Because errors of aminoacylation are known to be deleterious to cell growth, structure-specific determinants constitute a powerful selective pressure to retain the format of the two-domain L-shaped tRNA. ..
  30. Guo M, Chong Y, Shapiro R, Beebe K, Yang X, Schimmel P. Paradox of mistranslation of serine for alanine caused by AlaRS recognition dilemma. Nature. 2009;462:808-12 pubmed publisher
    ..The results reveal unconventional problems and solutions arising from the historical design of the protein synthesis machinery. ..
  31. McClain W, Gabriel K, Schneider J. Specific function of a G.U wobble pair from an adjacent helical site in tRNA(Ala) during recognition by alanyl-tRNA synthetase. RNA. 1996;2:105-9 pubmed
    ..We find, as in the original experiment, that a shifted G.U confers Ala acceptor activity. Moreover, the modified tRNA(Lys) was specific for Ala, corroborating our original conclusion and making it more compelling. ..
  32. Dignam J, Dignam S, Brumley L. Alanyl-tRNA synthetase from Escherichia coli, Bombyx mori and Ratus ratus. Existence of common structural features. Eur J Biochem. 1991;198:201-10 pubmed
    ..Circular dichroism spectra obtained for the three enzymes were qualitatively and quantitatively similar. There is some similarity in amino acid composition between the rat and insect enzymes. ..
  33. Gupta R. The phylogeny of proteobacteria: relationships to other eubacterial phyla and eukaryotes. FEMS Microbiol Rev. 2000;24:367-402 pubmed
    ..These signatures generally support the origin of mitochondria from an alpha-proteobacterium and provide evidence that the nuclear cytosolic homologs of many genes are also derived from proteobacteria. ..
  34. Beuning P, Yang F, Schimmel P, Musier Forsyth K. Specific atomic groups and RNA helix geometry in acceptor stem recognition by a tRNA synthetase. Proc Natl Acad Sci U S A. 1997;94:10150-4 pubmed
    ..By implication, the activity of mutant tRNAs measured in the in vivo assays appears to be more dependent on factors other than aminoacylation kinetic efficiency. ..
  35. Viswanathan S, Dignam S, Dignam J. Control of the levels of alanyl-, glycyl-, and seryl-tRNA synthetases in the silkgland of Bombyx mori. Dev Biol. 1988;129:350-7 pubmed
    ..A form of alanyl-tRNA synthetase with a slightly higher apparent molecular weight is detected in the posterior silkgland early in the fifth instar and in ovarian tissue. ..
  36. Mireau H, Lancelin D, Small I. The same Arabidopsis gene encodes both cytosolic and mitochondrial alanyl-tRNA synthetases. Plant Cell. 1996;8:1027-39 pubmed
    ..We conclude that the ALATS gene encodes both the cytosolic and the mitochondrial forms of AlaRS, depending on which of the two AUG codons is used to initiate translation. ..
  37. Sardesai N, Green R, Schimmel P. Efficient 50S ribosome-catalyzed peptide bond synthesis with an aminoacyl minihelix. Biochemistry. 1999;38:12080-8 pubmed
    ..These results are consistent with the minihelix domain being the major loci for tRNA interactions with the 50S ribosome. They may also have implications for the historical development of RNA-based systems of peptide synthesis. ..
  38. Garcia Lozano J, Gonzalez Escribano M, Rodriguez R, Rodriguez Sanchez J, Targoff I, Wichmann I, et al. Detection of anti-PL-12 autoantibodies by ELISA using a recombinant antigen; study of the immunoreactive region. Clin Exp Immunol. 1998;114:161-5 pubmed
    ..We conclude that ELISA using recombinant protein is an effective and useful method for routine screening for anti-PL-12 autoantibodies. ..
  39. Huang H, Kuei Y, Chao H, Chen S, Yeh L, Wang C. Cross-species and cross-compartmental aminoacylation of isoaccepting tRNAs by a class II tRNA synthetase. J Biol Chem. 2006;281:31430-9 pubmed
    ..albicans has evolved an unusual pattern of translation initiation and protein partitioning and codes for protein isoforms that can aminoacylate isoaccepting tRNAs from a different species and from across cellular compartments. ..
  40. Frederick C, Wang A, Rich A, Regan L, Schimmel P. Crystallization of a small fragment of an aminoacyl tRNA synthetase. J Mol Biol. 1988;203:521-2 pubmed
    ..The crystals grow in the presence of alanine as rhombic plates in space group P2(1)2(1)2(1) and with unit cell dimensions of a = 67.9 A, b = 98.5 A and c = 123.6 A (1 A = 0.1 nm). They diffract to better than 3 A resolution. ..
  41. Munoz R, Rossello Mora R, Amann R. Revised phylogeny of Bacteroidetes and proposal of sixteen new taxa and two new combinations including Rhodothermaeota phyl. nov. Syst Appl Microbiol. 2016;39:281-96 pubmed publisher
    ..nov., Thermonemataceae fam. nov. and Persicobacteraceae fam. nov.), as well as one new phylum Rhodothermaeota phyl. nov. that contains two classes, two orders, four families and a new genus with two new combinations. ..
  42. Barends S, Karzai A, Sauer R, Wower J, Kraal B. Simultaneous and functional binding of SmpB and EF-Tu-TP to the alanyl acceptor arm of tmRNA. J Mol Biol. 2001;314:9-21 pubmed
    ..Therefore, SmpB may function as an essential modulator of the tRNA-like acceptor arm of tmRNA during its successive steps in trans-translation. ..
  43. Griffiths E, Gupta R. The use of signature sequences in different proteins to determine the relative branching order of bacterial divisions: evidence that Fibrobacter diverged at a similar time to Chlamydia and the Cytophaga-Flavobacterium-Bacteroides division. Microbiology. 2001;147:2611-22 pubmed publisher
    ..succinogenes homologues. These results provide evidence that F. succinogenes does not belong to the proteobacterial division and thus should be placed in a similar position as the Chlamydia and CFB groups of species...
  44. Wolfson A, Pleiss J, Uhlenbeck O. A new assay for tRNA aminoacylation kinetics. RNA. 1998;4:1019-23 pubmed
  45. Griffiths E, Gupta R. Signature sequences in diverse proteins provide evidence for the late divergence of the Order Aquificales. Int Microbiol. 2004;7:41-52 pubmed
  46. Naganuma M, Sekine S, Chong Y, Guo M, Yang X, Gamper H, et al. The selective tRNA aminoacylation mechanism based on a single G•U pair. Nature. 2014;510:507-11 pubmed publisher
    ..This novel mechanism enables the single wobble pair to dominantly determine the specificity of tRNA selection, by an approximate 100-fold difference in kcat. ..
  47. Satoh S, Hirakata M, Suwa A, Mimori T, Inada S, Akizuki M. [Two cases of interstitial pneumonia with anti-PL-12 (alanyl tRNA synthetase) antibodies]. Ryumachi. 1996;36:862-8 pubmed
    ..However, the clinical significance of anti-PL-12 has not been examined in Japanese patients. These patients suggested that anti-PL-12 antibodies have a stronger association with IP than myositis in Japanese patients. ..
  48. Mimori T, Matsumura M, Ishida M, Takahashi Y, Hirakata M, Ohosone Y. [Analysis of autoantigens and clinical significance of antinuclear antibodies]. Rinsho Byori. 1998;46:303-10 pubmed
    ..Novel autoantibodies to tRNAs appeared to be associated with common clinical features but were distinct from previously described anti-aminoacyl-tRNA synthetases. ..
  49. Corvaisier S, Bordeau V, Felden B. Inhibition of transfer messenger RNA aminoacylation and trans-translation by aminoglycoside antibiotics. J Biol Chem. 2003;278:14788-97 pubmed
    ..SmpB and elongation factor Tu have RNA chaperone activities, ensuring that tmRNA adopts an optimal conformation during aminoacylation. ..
  50. Fukunaga R, Yokoyama S. Crystallization and preliminary X-ray crystallographic study of alanyl-tRNA synthetase from the archaeon Archaeoglobus fulgidus. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2007;63:224-8 pubmed
    ..15, c = 124.24 A. For the C-terminal fragment, a SeMet MAD data set was collected to 3.2 A resolution. The crystal belongs to the orthorhombic space group P222(1), with unit-cell parameters a = 124.15, b = 131.91, c = 138.68 A. ..
  51. O Neill G, Chen M, Soll D. delta-Aminolevulinic acid biosynthesis in Escherichia coli and Bacillus subtilis involves formation of glutamyl-tRNA. FEMS Microbiol Lett. 1989;51:255-9 pubmed
    ..coli and B. subtilis thus appears to be very similar to the pathway found in cyanobacteria, certain obligate anaerobic eubacteria, archaebacteria and in the chloroplasts of algae and higher plant species. ..
  52. Pleiss J, Wolfson A, Uhlenbeck O. Mapping contacts between Escherichia coli alanyl tRNA synthetase and 2' hydroxyls using a complete tRNA molecule. Biochemistry. 2000;39:8250-8 pubmed
    ..Contacts at similar sites in the T-loop are seen in the cocrystal structure of tRNA(Ser) and Thermus thermophilus seryl-tRNA synthetase. ..
  53. Musier Forsyth K, Usman N, Scaringe S, Doudna J, Green R, Schimmel P. Specificity for aminoacylation of an RNA helix: an unpaired, exocyclic amino group in the minor groove. Science. 1991;253:784-6 pubmed
    ..The results of these experiments indicate that an unpaired guanine 2-amino group at a specific position in the minor groove of an RNA helix marks a molecule for aminoacylation with alanine. ..