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Synthetic and Editing Mechanisms of Aminoacyl-tRNA Synthetases

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Aminoacyl-tRNA Synthetases in Biology and Medicine

Part of the book series: Topics in Current Chemistry ((TOPCURRCHEM,volume 344))

Abstract

Aminoacyl-tRNA synthetases (aaRS) ensure the faithful transmission of genetic information in all living cells. The 24 known aaRS families are divided into 2 structurally distinct classes (class I and class II), each featuring a catalytic domain with a common fold that binds ATP, amino acid, and the 3′-terminus of tRNA. In a common two-step reaction, each aaRS first uses the energy stored in ATP to synthesize an activated aminoacyl adenylate intermediate. In the second step, either the 2′- or 3′-hydroxyl oxygen atom of the 3′-A76 tRNA nucleotide functions as a nucleophile in synthesis of aminoacyl-tRNA. Ten of the 24 aaRS families are unable to distinguish cognate from noncognate amino acids in the synthetic reactions alone. These enzymes possess additional editing activities for hydrolysis of misactivated amino acids and misacylated tRNAs, with clearance of the latter species accomplished in spatially separate post-transfer editing domains. A distinct class of trans-acting proteins that are homologous to class II editing domains also perform hydrolytic editing of some misacylated tRNAs. Here we review essential themes in catalysis with a view toward integrating the kinetic, stereochemical, and structural mechanisms of the enzymes. Although the aaRS have now been the subject of investigation for many decades, it will be seen that a significant number of questions regarding fundamental catalytic functioning still remain unresolved.

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Abbreviations

AA-AMP:

Aminoacyl-AMP

aaRS:

Aminoacyl-tRNA synthetase

LUCA:

Last universal common ancestor

MARS:

Multi-tRNA synthetase complex

UAA:

Unnatural amino acid

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Acknowledgments

We thank Nevena Cvetesic and Andrew Hadd for assistance with figures. This work was supported by the National Institutes of Health (GM63713 and 1RO3TW008024) and by the Croatian Science Foundation (grant 09.01/293). I.G.S. thanks the Adris foundation for support.

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Authors and Affiliations

  1. Department of Chemistry, Portland State University, 751, Portland, OR, 97207, USA

    John J. Perona

  2. Department of Biochemistry & Molecular Biology, Oregon Health & Sciences University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA

    John J. Perona

  3. Faculty of Science, Department of Chemistry, University of Zagreb, Horvatovac 102a, 10000, Zagreb, Croatia

    Ita Gruic-Sovulj

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  1. John J. Perona
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  2. Ita Gruic-Sovulj
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Correspondence to John J. Perona .

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  1. Department of Molecular Medicine and Biopharmaceutical Sciences, Medicinal Bioconvergence Research Center, College of Pharmacy, Seoul National University, Korea, Republic of (South Korea)

    Sunghoon Kim

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Perona, J.J., Gruic-Sovulj, I. (2013). Synthetic and Editing Mechanisms of Aminoacyl-tRNA Synthetases. In: Kim, S. (eds) Aminoacyl-tRNA Synthetases in Biology and Medicine. Topics in Current Chemistry, vol 344. Springer, Dordrecht. https://doi.org/10.1007/128_2013_456

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