ArticleNature2009
Paradox of mistranslation of serine for alanine caused by AlaRS recognition dilemma.
Article in Nature, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed.
- Article
- Covalent allosteric inhibition of AARS1 lactyltransferase.Nature communications · 2026Article
- Translation accuracy in E. coli.Nucleic acids research · 2026Article
- Aminoacyl-tRNA-dependent enzymes in natural product biosynthesis: structure-function insights.The Journal of antibiotics · 2026Review
- The role of Alanyl-tRNA synthetase 1 lactylation in tumors and other diseases.Discover oncology · 2026Review
- A conserved editing mechanism for the fidelity of bacterial cell wall biosynthesis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Unlocking the serine mischarging paradox and inhibiting lactyltransferase activity of AlaRS by a single-point mutation.Nucleic acids research · 2025Article
- Unexpected enzymatic function of an ancient nucleic acid-binding fold.Nucleic acids research · 2025Article
- Emerging roles of lysine lactyltransferases and lactylation.Nature cell biology · 2025Review
- Yeast models for Charcot-Marie-Tooth disease-causing aminoacyl-tRNA synthetase alleles reveal the cellular basis of disease.IUBMB life · 2025Review
- AARS Online: A collaborative database on the structure, function, and evolution of the aminoacyl-tRNA synthetases.IUBMB life · 2024Article
- Strategies for detecting aminoacylation and aminoacyl-tRNA editingIsrael journal of chemistry · 2024Article
- Eukaryotic AlaX provides multiple checkpoints for quality and quantity of aminoacyl-tRNAs in translation.Nucleic acids research · 2024Article
- Design principles and functional basis of enantioselectivity of alanyl-tRNA synthetase and a chiral proofreader during protein biosynthesis.Nucleic acids research · 2023Article
- Sequential magnesium binding facilitates lysyl-tRNA synthetase to recognize ATP.Biochemistry and biophysics reports · 2023Article
- Peptide Bond Formation between Aminoacyl-Minihelices by a Scaffold Derived from the Peptidyl Transferase Center.Life (Basel, Switzerland) · 2022Article
- Impact of alanyl-tRNA synthetase editing deficiency in yeast.Nucleic acids research · 2021Article
- A molecular link between cell wall biosynthesis, translation fidelity, and stringent response inProceedings of the National Academy of Sciences of the United States of America · 2021Article
- CMT2N-causing aminoacylation domain mutants enable Nrp1 interaction with AlaRS.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Fine-Tuning of Alanyl-tRNA Synthetase Quality Control Alleviates Global Dysregulation of the Proteome.Genes · 2020Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Mistranslation arising from confusion of serine for alanine by alanyl-tRNA synthetases (AlaRSs) has profound functional consequences. Throughout evolution, two editing checkpoints prevent disease-causing mistranslation from confusing glycine or serine for alanine at the active site of AlaRS. In both bacteria and mice, Ser poses a bigger challenge than Gly. One checkpoint is the AlaRS editing centre, and the other is from widely distributed AlaXps-free-standing, genome-encoded editing proteins that clear Ser-tRNA(Ala). The paradox of misincorporating both a smaller (glycine) and a larger (serine) amino acid suggests a deep conflict for nature-designed AlaRS. Here we show the chemical basis for this conflict. Nine crystal structures, together with kinetic and mutational analysis, provided snapshots of adenylate formation for each amino acid. An inherent dilemma is posed by constraints of a structural design that pins down the alpha-amino group of the bound amino acid by using an acidic residue. This design, dating back more than 3 billion years, creates a serendipitous interaction with the serine OH that is difficult to avoid. Apparently because no better architecture for the recognition of alanine could be found, the serine misactivation problem was solved through free-standing AlaXps, which appeared contemporaneously with early AlaRSs. The results reveal unconventional problems and solutions arising from the historical design of the protein synthesis machinery.
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