ArticleACS chemical biology2011
Stereochemical basis for engineered pyrrolysyl-tRNA synthetase and the efficient in vivo incorporation of structurally divergent non-native amino acids.
Article in ACS chemical biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
63 citing papers in PubMed, 103 citations in OpenAlex.
- Expanding the genetic code: phage-driven evolution of pyrrolysyl-synthetase for site-specific incorporation of synthetic phenylalanine and tyrosine derivatives.Frontiers in molecular biosciences · 2026Article
- Strategies to Expand the Genetic Code of Mammalian Cells.Chemical reviews · 2025Review
- Optogenetics with Atomic Precision─A Comprehensive Review of Optical Control of Protein Function through Genetic Code Expansion.Chemical reviews · 2025Review
- Pyrrolysine Aminoacyl-tRNA Synthetase as a Tool for Expanding the Genetic Code.International journal of molecular sciences · 2025Review
- Engineering Pyrrolysine Systems for Genetic Code Expansion and Reprogramming.Chemical reviews · 2024Review
- Genetically Encoded Epoxide Warhead for Precise and Versatile Covalent Targeting of Proteins.Journal of the American Chemical Society · 2024Article
- Expanding the Genetic Code ofACS chemical biology · 2024Article
- Probing the conformational dynamics of thiol-isomerases using non-canonical amino acids and single-molecule FRET.Methods (San Diego, Calif.) · 2023Article
- Crystal Structure of Pyrrolysyl-tRNA Synthetase from a Methanogenic Archaeon ISO4-G1 and Its Structure-Based Engineering for Highly-Productive Cell-Free Genetic Code Expansion with Non-Canonical Amino Acids.International journal of molecular sciences · 2023Article
- Update of the Pyrrolysyl-tRNA Synthetase/tRNAJournal of bacteriology · 2023Review
- Chemically Acylated tRNAs are Functional in Zebrafish Embryos.Journal of the American Chemical Society · 2023Article
- Focused Engineering of Pyrrolysyl-tRNA Synthetase-Based Orthogonal Translation Systems for the Incorporation of Various Noncanonical Amino Acids.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Genetically encoded chemical crosslinking of carbohydrate.Nature chemistry · 2023Article
- Encoding latent SuFEx reactive meta-fluorosulfate tyrosine to expand covalent bonding of proteins.Chemical communications (Cambridge, England) · 2022Article
- A Designed, Highly Efficient Pyrrolysyl-tRNA Synthetase Mutant Binds o-Chlorophenylalanine Using Two Halogen Bonds.Journal of molecular biology · 2022Article
- Expanding the functionality of proteins with genetically encoded dibenzo[Chemical science · 2022Article
- Making Sense of "Nonsense" and More: Challenges and Opportunities in the Genetic Code Expansion, in the World of tRNA Modifications.International journal of molecular sciences · 2022Review
- Rational incorporation of any unnatural amino acid into proteins by machine learning on existing experimental proofs.Computational and structural biotechnology journal · 2022Article
- Engineering Pyrrolysyl-tRNA Synthetase for the Incorporation of Non-Canonical Amino Acids with Smaller Side Chains.International journal of molecular sciences · 2021Article
- A Genetically Encoded Fluorosulfonyloxybenzoyl-l-lysine for Expansive Covalent Bonding of Proteins via SuFEx Chemistry.Journal of the American Chemical Society · 2021Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Unnatural amino acids (Uaas) can be translationally incorporated into proteins in vivo using evolved tRNA/aminoacyl-tRNA synthetase (RS) pairs, affording chemistries inaccessible when restricted to the 20 natural amino acids. To date, most evolved RSs aminoacylate Uaas chemically similar to the native substrate of the wild-type RS; these conservative changes limit the scope of Uaa applications. Here, we adapt Methanosarcina mazei PylRS to charge a noticeably disparate Uaa, O-methyl-l-tyrosine (Ome). In addition, the 1.75 Å X-ray crystal structure of the evolved PylRS complexed with Ome and a non-hydrolyzable ATP analogue reveals the stereochemical determinants for substrate selection. Catalytically synergistic active site mutations remodel the substrate-binding cavity, providing a shortened but wider active site. In particular, mutation of Asn346, a residue critical for specific selection and turnover of the Pyl chemical core, accommodates different side chains while the central role of Asn346 in aminoacylation is rescued through compensatory hydrogen bonding provided by A302T. This multifaceted analysis provides a new starting point for engineering PylRS to aminoacylate a significantly more diverse selection of Uaas than previously anticipated.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.