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Gene Review

alaS  -  alanyl-tRNA synthetase

Escherichia coli O157:H7 str. Sakai

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Disease relevance of ECs3554

  • Escherichia coli alanyl-tRNA synthetase contains a zinc-binding Cys-Xaa2-Cys-Xaa6-His-Xaa2-His motif that resembles that of retroviral nucleic acid binding proteins [1].
  • Although this motif in E. coli alanyl-tRNA synthetase is of a different size than and has only two sequence identities with the analogous motif in yeast aspartyl- and Thermus thermophilus seryl-tRNA synthetases, whose structures are known, the functional consequences of the mutations are explainable in terms of those structures [2].

High impact information on ECs3554

  • Class II may also contain AlaRS and GlyRS, because these sequences have a typical motif 3 [3].
  • Docking of tRNA(Ala) on AlaRS shows critical contacts with the three domains, consistent with previous mutagenesis and functional data [4].
  • Early work on aminoacylation of alanine-specific tRNA (tRNA(Ala)) by alanyl-tRNA synthetase (AlaRS) gave rise to the concept of an early "second genetic code" imbedded in the acceptor stems of tRNAs [4].
  • When applied to Escherichia coli alanyl-tRNA synthetase, the assay allowed accurate measurement of aminoacylation of the most deleterious mutants of tRNA(Ala) [5].
  • The correlation between functional and structural data suggests that the G.U pair provides a distinctive structure and a point of deformability that allow the tRNA acceptor end to fit into the active site of the alanyl-tRNA synthetase [6].

Chemical compound and disease context of ECs3554

  • Previous work showed that the transfer of alanine from Escherichia coli alanyl-tRNA synthetase to a cognate RNA minihelix involves a transition state sensitive to changes in the tRNA acceptor stem [7].
  • The invariant arginine in motif 2 of Escherichia coli alanyl-tRNA synthetase is important for catalysis but not for substrate binding [8].
  • Lysine73, located in the adenylate synthesis domain of Escherichia coli alanyl-tRNA synthetase (AlaRS), was previously indicated to be an important residue for the interaction of this enzyme with the acceptor stem of its cognate tRNA (tRNA(Ala)) [9].
  • Synthesis of an mRNA fragment of alanyl-tRNA synthetase gene in Escherichia coli using the 6-methyl-3-pyridyl group for protection of the imide functions of uridine and guanosine [10].

Biological context of ECs3554

  • Site-directed random mutagenesis has been employed to generate a set of proteins containing amino acid substitutions in a portion of motif 2 of AlaRS [8].
  • It was previously shown that recognition by AlaRS is severely affected by a simple base pair transversion of the G2:C71 pair at the second position in the RNA helix [11].
  • Kinetic parameters of tRNA aminoacylation by Escherichia coli AlaRS obtained by the new method are in excellent agreement with those measured by the conventional method [12].
  • Alanyl-tRNA synthetase (AlaRS) from Escherichia coli is a multimeric enzyme that catalyzes the esterification of alanine to tRNA(Ala) in the ATP-dependent aminoacylation reaction [13].
  • The relative genetic position of the following four mutations of ribosomal protein S5 has been determined: spc-13, a mutation to spectinomycin resistance; stri N421 and strid1023, mutations suppressing dependence on streptomycin and sup0-1, a mutation suppressing partially the temperature-sensitive phenotype of an alanyl-tRNA synthetase mutation [14].

Anatomical context of ECs3554

  • The function of SmpB protein in the trans-translation system was evaluated using the well-defined cell-free translation system consisting of purified ribosome, alanyl-tRNA synthetase and elongation factors [15].

Associations of ECs3554 with chemical compounds

  • A cysteine in the C-terminal region of alanyl-tRNA synthetase is important for aminoacylation activity [13].
  • In the case of mild DTNB treatment, only two of the six cysteines in AlaRS are modified, with release of all zinc and partial loss of aminoacylation activity [13].
  • The assay is based on coupling the alanyl-tRNA synthetase-dependent formation of AMP to the lactate dehydrogenase oxidation of NADH [16].
  • Furthermore, urea denaturation experiments demonstrate the role of zinc in stabilization of AlaRS structure [17].
  • Replacement of this residue with glutamine produced a reduction in the catalytic efficiency of AlaRS in the aminoacylation assay, primarily through an increase in the apparent KM for tRNA(Ala) [Hill, K., and Schimmel, P. (1989) Biochemistry 28, 2577-2586] [9].

Other interactions of ECs3554

  • Analysis of the different mutants revealed (or confirmed for some nucleotides) their role as positive and/or negative determinants in AlaRS, LysRS, and ArgRS recognition [18].
  • Here it is shown that HisRS and TrpRS (Bacillus stearothermophilus) and AlaRS (E. coli) also synthesize the hybrid compounds Ap4G, Ap4C, and Ap4U [19].

Analytical, diagnostic and therapeutic context of ECs3554

  • Northern blot analysis indicated that the mRNA for alanyl-tRNA synthetase is 3.8 kilobase pairs in mRNA isolated from posterior silk gland, middle silk gland, and ovarian tissue [20].


  1. A retroviral-like metal binding motif in an aminoacyl-tRNA synthetase is important for tRNA recognition. Miller, W.T., Schimmel, P. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  2. Functional dissection of a predicted class-defining motif in a class II tRNA synthetase of unknown structure. Davis, M.W., Buechter, D.D., Schimmel, P. Biochemistry (1994) [Pubmed]
  3. Partition of tRNA synthetases into two classes based on mutually exclusive sets of sequence motifs. Eriani, G., Delarue, M., Poch, O., Gangloff, J., Moras, D. Nature (1990) [Pubmed]
  4. Alanyl-tRNA synthetase crystal structure and design for acceptor-stem recognition. Swairjo, M.A., Otero, F.J., Yang, X.L., Lovato, M.A., Skene, R.J., McRee, D.E., Ribas de Pouplana, L., Schimmel, P. Mol. Cell (2004) [Pubmed]
  5. Modulation of tRNAAla identity by inorganic pyrophosphatase. Wolfson, A.D., Uhlenbeck, O.C. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  6. Correlation of deformability at a tRNA recognition site and aminoacylation specificity. Chang, K.Y., Varani, G., Bhattacharya, S., Choi, H., McClain, W.H. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  7. Identification of discriminator base atomic groups that modulate the alanine aminoacylation reaction. Fischer, A.E., Beuning, P.J., Musier-Forsyth, K. J. Biol. Chem. (1999) [Pubmed]
  8. The invariant arginine in motif 2 of Escherichia coli alanyl-tRNA synthetase is important for catalysis but not for substrate binding. Lu, Y., Hill, K.A. J. Biol. Chem. (1994) [Pubmed]
  9. Amino acid substitutions at position 73 in motif 2 of Escherichia coli alanyl-tRNA synthetase. Filley, S.J., Hill, K.A. Arch. Biochem. Biophys. (1993) [Pubmed]
  10. Synthesis of an mRNA fragment of alanyl-tRNA synthetase gene in Escherichia coli using the 6-methyl-3-pyridyl group for protection of the imide functions of uridine and guanosine. Welch, C.J., Zhou, X.X., Chattopadhyaya, J. Acta Chem. Scand., B, Org. Chem. Biochem. (1986) [Pubmed]
  11. Efficient aminoacylation of the tRNA(Ala) acceptor stem: dependence on the 2:71 base pair. Beuning, P.J., Nagan, M.C., Cramer, C.J., Musier-Forsyth, K., Gelpí, J.L., Bashford, D. RNA (2002) [Pubmed]
  12. A new assay for tRNA aminoacylation kinetics. Wolfson, A.D., Pleiss, J.A., Uhlenbeck, O.C. RNA (1998) [Pubmed]
  13. A cysteine in the C-terminal region of alanyl-tRNA synthetase is important for aminoacylation activity. Wu, M.X., Filley, S.J., Xiong, J., Lee, J.J., Hill, K.A. Biochemistry (1994) [Pubmed]
  14. Genetic position and amino acid replacements of several mutations in ribosomal protein S5 from Escherichia coli. Piepersberg, W., Böck, A., Yaguchi, M., Wittmann, H.G. Mol. Gen. Genet. (1975) [Pubmed]
  15. The role of SmpB protein in trans-translation. Shimizu, Y., Ueda, T. FEBS Lett. (2002) [Pubmed]
  16. A continuous spectrophotometric assay for the aminoacylation of transfer RNA by alanyl-transfer RNA synthetase. Wu, M.X., Hill, K.A. Anal. Biochem. (1993) [Pubmed]
  17. Characterization of zinc-depleted alanyl-tRNA synthetase from Escherichia coli: role of zinc. Sood, S.M., Wu, M.X., Hill, K.A., Slattery, C.W. Arch. Biochem. Biophys. (1999) [Pubmed]
  18. Selection of tRNA(Asp) amber suppressor mutants having alanine, arginine, glutamine, and lysine identity. Martin, F., Reinbolt, J., Dirheimer, G., Gangloff, J., Eriani, G. RNA (1996) [Pubmed]
  19. Synthesis of hybrid bisnucleoside 5',5"'-P1,P4-tetraphosphates by aminoacyl-tRNA synthetases. Traut, T.W. Mol. Cell. Biochem. (1987) [Pubmed]
  20. Primary structure of alanyl-tRNA synthetase and the regulation of its mRNA levels in Bombyx mori. Chang, P.K., Dignam, J.D. J. Biol. Chem. (1990) [Pubmed]
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