ArticleProceedings of the National Academy of Sciences of the United States of America2014
Polyspecific pyrrolysyl-tRNA synthetases from directed evolution.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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Who cites it
82 citing papers in PubMed.
- Comparative evaluation of noncanonical amino acids as site-specific NMR probes for the complex of E. coli SSB with single-stranded DNA without isotope labelling.The FEBS journal · 2026Article
- Genetic Incorporation of Diverse Noncanonical Amino Acids for Histidine Substitution.Journal of the American Chemical Society · 2026Article
- Mistranslation from an endogenous tRNA variant in human pan-genome cell lines.Nucleic acids research · 2026Article
- Machine learning-guided evolution of pyrrolysyl-tRNA synthetase for improved incorporation efficiency of diverse noncanonical amino acids.Nature communications · 2025Article
- Transfer RNA and small molecule therapeutics for aminoacyl-tRNA synthetase diseases.The FEBS journal · 2025Review
- Computationally Assisted Noncanonical Amino Acid Incorporation.ACS central science · 2025Article
- Pyrrolysine Aminoacyl-tRNA Synthetase as a Tool for Expanding the Genetic Code.International journal of molecular sciences · 2025Review
- Article
- Reaching New Heights in Genetic Code Manipulation with High Throughput Screening.Chemical reviews · 2024Review
- Engineering Pyrrolysine Systems for Genetic Code Expansion and Reprogramming.Chemical reviews · 2024Review
- Cracking the Code: Reprogramming the Genetic Script in Prokaryotes and Eukaryotes to Harness the Power of Noncanonical Amino Acids.Chemical reviews · 2024Review
- Evolution of Pyrrolysyl-tRNA Synthetase: From Methanogenesis to Genetic Code Expansion.Chemical reviews · 2024Review
- Genetic Encoding of Phosphorylated Amino Acids into Proteins.Chemical reviews · 2024Review
- Bacteria employ lysine acetylation of transcriptional regulators to adapt gene expression to cellular metabolism.Nature communications · 2024Article
- tRNA shape is an identity element for an archaeal pyrrolysyl-tRNA synthetase from the human gut.Nucleic acids research · 2024Article
- Article
- An evolved pyrrolysyl-tRNA synthetase with polysubstrate specificity expands the toolbox for engineering enzymes with incorporation of noncanonical amino acids.Bioresources and bioprocessing · 2023Article
- Expanding the substrate scope of pyrrolysyl-transfer RNA synthetase enzymes to include non-α-amino acids in vitro and in vivo.Nature chemistry · 2023Article
- Orthogonal translation with 5-cyanotryptophan as an infrared probe for local structural information, electrostatics, and hydrogen bonding.Protein science : a publication of the Protein Society · 2023Article
- Site-specific encoding of photoactivity and photoreactivity into antibody fragments.Nature chemical biology · 2023Article
22 more citing papers are in PubMed but not listed here.
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10 authors.
Funding
Abstract
Pyrrolysyl-tRNA synthetase (PylRS) and its cognate tRNA(Pyl) have emerged as ideal translation components for genetic code innovation. Variants of the enzyme facilitate the incorporation >100 noncanonical amino acids (ncAAs) into proteins. PylRS variants were previously selected to acylate N(ε)-acetyl-Lys (AcK) onto tRNA(Pyl). Here, we examine an N(ε)-acetyl-lysyl-tRNA synthetase (AcKRS), which is polyspecific (i.e., active with a broad range of ncAAs) and 30-fold more efficient with Phe derivatives than it is with AcK. Structural and biochemical data reveal the molecular basis of polyspecificity in AcKRS and in a PylRS variant [iodo-phenylalanyl-tRNA synthetase (IFRS)] that displays both enhanced activity and substrate promiscuity over a chemical library of 313 ncAAs. IFRS, a product of directed evolution, has distinct binding modes for different ncAAs. These data indicate that in vivo selections do not produce optimally specific tRNA synthetases and suggest that translation fidelity will become an increasingly dominant factor in expanding the genetic code far beyond 20 amino acids.
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