ArticleNature chemical biology2012
Computational redesign of a mononuclear zinc metalloenzyme for organophosphate hydrolysis.
Article in Nature chemical biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 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
65 citing papers in PubMed, 209 citations in OpenAlex.
- Structure-activity relationships in catalytic amyloids.Journal of inorganic biochemistry · 2026Article
- Catalytic Mechanism of Collagen Hydrolysis by Zinc(II)-Dependent Matrix Metalloproteinase-1.The journal of physical chemistry. B · 2023Article
- Dan Tawfik's Lessons for Protein Engineers about Enzymes Adapting to New Substrates.Biochemistry · 2023Review
- Design of a Flexible, Zn-Selective Protein Scaffold that Displays Anti-Irving-Williams Behavior.Journal of the American Chemical Society · 2022Article
- Designing Artificial Metalloenzymes by Tuning of the Environment beyond the Primary Coordination Sphere.Chemical reviews · 2022Review
- Introducing a New Bond-Forming Activity in an Archaeal DNA Polymerase by Structure-Guided Enzyme Redesign.ACS chemical biology · 2022Article
- Article
- Facilitating Machine Learning-Guided Protein Engineering with Smart Library Design and Massively Parallel Assays.Advanced genetics (Hoboken, N.J.) · 2021Article
- Enhanced chemoselectivity of a plant cytochrome P450 through protein engineering of surface and catalytic residues.aBIOTECH · 2021Article
- Engineering the protein dynamics of an ancestral luciferase.Nature communications · 2021Article
- Extension of an Atom-Atom Dispersion Function to Halogen Bonds and Its Use for Rational Design of Drugs and Biocatalysts.The journal of physical chemistry. A · 2021Article
- Bottom-Up Nonempirical Approach To Reducing Search Space in Enzyme Design Guided by Catalytic Fields.Journal of chemical theory and computation · 2020Article
- Unlocking the therapeutic potential of artificial metalloenzymes.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2020Review
- MinimalistACS catalysis · 2019Article
- Artificial Metalloenzymes: Challenges and Opportunities.ACS central science · 2019Review
- Article
- Automated Design of Efficient and Functionally Diverse Enzyme Repertoires.Molecular cell · 2018Article
- In silico design of potentially functional artificial metallo-haloalkane dehalogenase containing catalytic zinc.3 Biotech · 2018Article
- Expanding the boundary of biocatalysis: design and optimization of in vitro tandem catalytic reactions for biochemical production.Critical reviews in biochemistry and molecular biology · 2018Review
- Design of artificial metalloproteins/metalloenzymes by tuning noncovalent interactions.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2018Review
5 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
Abstract
The ability to redesign enzymes to catalyze noncognate chemical transformations would have wide-ranging applications. We developed a computational method for repurposing the reactivity of metalloenzyme active site functional groups to catalyze new reactions. Using this method, we engineered a zinc-containing mouse adenosine deaminase to catalyze the hydrolysis of a model organophosphate with a catalytic efficiency (k(cat)/K(m)) of ~10(4) M(-1) s(-1) after directed evolution. In the high-resolution crystal structure of the enzyme, all but one of the designed residues adopt the designed conformation. The designed enzyme efficiently catalyzes the hydrolysis of the R(P) isomer of a coumarinyl analog of the nerve agent cyclosarin, and it shows marked substrate selectivity for coumarinyl leaving groups. Computational redesign of native enzyme active sites complements directed evolution methods and offers a general approach for exploring their untapped catalytic potential for new reactivities.
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.