ArticleProceedings of the National Academy of Sciences of the United States of America2014
Impact of scaffold rigidity on the design and evolution of an artificial Diels-Alderase.
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 48 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
48 citing papers in PubMed.
- Protein engineering: status report.Protein engineering, design & selection : PEDS · 2026Review
- Evolutionary Specialization of a Promiscuous Designer Enzyme.ACS catalysis · 2025Article
- Spiers Memorial Lecture: Engineering biocatalysts.Faraday discussions · 2024Article
- Strategies for designing biocatalysts with new functions.Chemical Society reviews · 2024Review
- A non-canonical nucleophile unlocks a new mechanistic pathway in a designed enzyme.Nature communications · 2024Article
- Efficient Base-Catalyzed Kemp Elimination in an Engineered Ancestral Enzyme.International journal of molecular sciences · 2022Article
- Catalysis and Electron Transfer inChemical reviews · 2022Review
- Derivatives of Natural Organocatalytic Cofactors and Artificial Organocatalytic Cofactors as Catalysts in Enzymes.Chembiochem : a European journal of chemical biology · 2022Review
- The road to fully programmable protein catalysis.Nature · 2022Review
- Mechanism of the Stereoselective Catalysis of Diels-Alderase PyrE3 Involved in Pyrroindomycin Biosynthesis.Journal of the American Chemical Society · 2022Article
- Evolution of dynamical networks enhances catalysis in a designer enzyme.Nature chemistry · 2021Article
- Exo-selective intermolecular Diels-Alder reaction by PyrI4 and AbnU on non-natural substrates.Communications chemistry · 2021Article
- Side Chain Conformation Restriction in the Catalysis of Glycosidic Bond Formation by Leloir Glycosyltransferases, Glycoside Phosphorylases, and Transglycosidases.ACS catalysis · 2021Article
- Acyl Transfer Catalytic Activity in De Novo Designed Protein with N-Terminus of α-Helix As Oxyanion-Binding Site.Journal of the American Chemical Society · 2021Article
- Efficient Lewis acid catalysis of an abiological reaction in a de novo protein scaffold.Nature chemistry · 2021Article
- How directed evolution reshapes the energy landscape in an enzyme to boost catalysis.Science (New York, N.Y.) · 2020Article
- Tight and specific lanthanide binding in a de novo TIM barrel with a large internal cavity designed by symmetric domain fusion.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Computational Investigation of the Mechanism of Diels-Alderase PyrI4.Journal of the American Chemical Society · 2020Article
- The physical origin of rate promoting vibrations in enzymes revealed by structural rigidity.Scientific reports · 2020Article
- A mechanistic view of enzyme evolution.Protein science : a publication of the Protein Society · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
By combining targeted mutagenesis, computational refinement, and directed evolution, a modestly active, computationally designed Diels-Alderase was converted into the most proficient biocatalyst for [4+2] cycloadditions known. The high stereoselectivity and minimal product inhibition of the evolved enzyme enabled preparative scale synthesis of a single product diastereomer. X-ray crystallography of the enzyme-product complex shows that the molecular changes introduced over the course of optimization, including addition of a lid structure, gradually reshaped the pocket for more effective substrate preorganization and transition state stabilization. The good overall agreement between the experimental structure and the original design model with respect to the orientations of both the bound product and the catalytic side chains contrasts with other computationally designed enzymes. Because design accuracy appears to correlate with scaffold rigidity, improved control over backbone conformation will likely be the key to future efforts to design more efficient enzymes for diverse chemical reactions.
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.