ArticleProceedings of the National Academy of Sciences of the United States of America2015
Exploring the potential impact of an expanded genetic code on protein function.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
35 citing papers in PubMed, 77 citations in OpenAlex.
- Sequence Display enables large-scale sequence-activity datasets for rapid protein evolution.Nature biotechnology · 2026Article
- Structural comparison of substrate-binding pockets of serine β-lactamases in classes A, C, and D.Journal of enzyme inhibition and medicinal chemistry · 2025Review
- Design and evolution of artificial enzyme with in-situ biosynthesized non-canonical amino acid.Nature communications · 2025Article
- Biosynthesis of Unnatural Cyclodipeptides through Genetic Code Expansion and Cyclodipeptide Synthase Evolution.Journal of the American Chemical Society · 2025Article
- Biosynthesis of Halogenated Tryptophans for Protein Engineering Using Genetic Code Expansion.Chembiochem : a European journal of chemical biology · 2024Article
- Noncanonical Amino Acids: Bringing New-to-Nature Functionalities to Biocatalysis.Chemical reviews · 2024Review
- Synthesis at the Interface of Chemistry and Biology.Accounts of chemical research · 2024Review
- Noncanonical Amino Acids in Biocatalysis.Chemical reviews · 2024Review
- Directed evolution of the fluorescent protein CGP withApplied and environmental microbiology · 2024Article
- Fluorosulfate as a Latent Sulfate in Peptides and Proteins.Journal of the American Chemical Society · 2023Article
- Artificial Small Molecules as Cofactors and Biomacromolecular Building Blocks in Synthetic Biology: Design, Synthesis, Applications, and Challenges.Molecules (Basel, Switzerland) · 2023Review
- Allosteric inhibition of TEM-1 β lactamase: Microsecond molecular dynamics simulations provide mechanistic insights.Protein science : a publication of the Protein Society · 2023Article
- Chemically Modified Bacterial Sacculi as a Vaccine Microparticle Scaffold.ACS chemical biology · 2022Article
- Biosynthesis and Genetic Incorporation of 3,4-Dihydroxy-L-Phenylalanine into Proteins in Escherichia coli.Journal of molecular biology · 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
- Broadening the Toolkit for Quantitatively Evaluating Noncanonical Amino Acid Incorporation in Yeast.ACS synthetic biology · 2021Article
- Recent advancements in enzyme engineering via site-specific incorporation of unnatural amino acids.World journal of microbiology & biotechnology · 2021Review
- How To Quantify a Genetic Firewall? A Polarity-Based Metric for Genetic Code Engineering.Chembiochem : a European journal of chemical biology · 2021Article
- Enhancement of Activity and Thermostability of Keratinase FromFrontiers in bioengineering and biotechnology · 2021Article
- Development and Testing of Force Field Parameters for Phenylalanine and Tyrosine Derivatives.Frontiers in molecular biosciences · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
With few exceptions, all living organisms encode the same 20 canonical amino acids; however, it remains an open question whether organisms with additional amino acids beyond the common 20 might have an evolutionary advantage. Here, we begin to test that notion by making a large library of mutant enzymes in which 10 structurally distinct noncanonical amino acids were substituted at single sites randomly throughout TEM-1 β-lactamase. A screen for growth on the β-lactam antibiotic cephalexin afforded a unique p-acrylamido-phenylalanine (AcrF) mutation at Val-216 that leads to an increase in catalytic efficiency by increasing kcat, but not significantly affecting KM. To understand the structural basis for this enhanced activity, we solved the X-ray crystal structures of the ligand-free mutant enzyme and of the deacylation-defective wild-type and mutant cephalexin acyl-enzyme intermediates. These structures show that the Val-216-AcrF mutation leads to conformational changes in key active site residues-both in the free enzyme and upon formation of the acyl-enzyme intermediate-that lower the free energy of activation of the substrate transacylation reaction. The functional changes induced by this mutation could not be reproduced by substitution of any of the 20 canonical amino acids for Val-216, indicating that an expanded genetic code may offer novel solutions to proteins as they evolve new activities.
Indexed as
Identifiers
What OpenQuestion holds
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.