ArticleNature chemical biology2011
Directed evolution of hydrolases for prevention of G-type nerve agent intoxication.
Article in Nature chemical biology, 2011. 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, 200 citations in OpenAlex.
- Human CYP2C9 Metabolism of Organophosphorus Pesticides and Nerve Agent Surrogates.Journal of xenobiotics · 2025Article
- Gestational saccharin consumption disrupts gut-brain axis glucose homeostasis control in adolescent offspring rats in a sex-dependent manner.Biology of sex differences · 2025Article
- Role of paraoxonase 1 in organophosphate G-series nerve agent poisoning and future therapeutic strategies.Archives of toxicology · 2025Review
- Human Paraoxonase 1: From Bloodstream Enzyme to Disease Fighter & Therapeutic Intervention.Current protein & peptide science · 2025Review
- Coupling Peptide-Based Encapsulation of Enzymes with Bacteria for Paraoxon Bioremediation.ACS applied materials & interfaces · 2024Article
- Gene Cloning, Heterologous Expression, and In Silico Analysis of Chitinase B fromMolecules (Basel, Switzerland) · 2024Article
- Warfare Nerve Agents and Paraoxonase-1 as a Potential Prophylactic Therapy against Intoxication.Protein and peptide letters · 2024Review
- The impact of molecular variants, crystallization conditions and the space group on ligand-protein complexes: a case study on bacterial phosphotriesterase.Acta crystallographica. Section D, Structural biology · 2023Article
- Ultrahigh-Throughput Enzyme Engineering and Discovery inChemical reviews · 2023Review
- A primer to directed evolution: current methodologies and future directions.RSC chemical biology · 2023Review
- Targeted Metabolomics of Organophosphate Pesticides and Chemical Warfare Nerve Agent Simulants Using High- and Low-Dose Exposure in Human Liver Microsomes.Metabolites · 2023Article
- Dan Tawfik's Lessons for Protein Engineers about Enzymes Adapting to New Substrates.Biochemistry · 2023Review
- Advances in Noble-Metal Nanoparticle-Based Fluorescence Detection of Organophosphorus Chemical Warfare Agents.ACS omega · 2022Review
- Utilization of diverse organophosphorus pollutants by marine bacteria.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Insights into the role of paraoxonase 2 in human pathophysiology.Journal of biosciences · 2022Article
- Droplet Microfluidics and Directed Evolution of Enzymes: An Intertwined Journey.Angewandte Chemie (International ed. in English) · 2021Review
- Substrate Analogues for the Enzyme-Catalyzed Detoxification of the Organophosphate Nerve Agents-Sarin, Soman, and Cyclosarin.Biochemistry · 2021Article
- Droplet flow cytometry for single-cell analysis.RSC advances · 2021Review
- Enzymes, Reacting with Organophosphorus Compounds as Detoxifiers: Diversity and Functions.International journal of molecular sciences · 2021Review
- Rapid, Biomimetic Degradation of a Nerve Agent Simulant by Incorporating Imidazole Bases into a Metal-Organic Framework.ACS catalysis · 2021Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Organophosphate nerve agents are extremely lethal compounds. Rapid in vivo organophosphate clearance requires bioscavenging enzymes with catalytic efficiencies of >10(7) (M(-1) min(-1)). Although serum paraoxonase (PON1) is a leading candidate for such a treatment, it hydrolyzes the toxic S(p) isomers of G-agents with very slow rates. We improved PON1's catalytic efficiency by combining random and targeted mutagenesis with high-throughput screening using fluorogenic analogs in emulsion compartments. We thereby enhanced PON1's activity toward the coumarin analog of S(p)-cyclosarin by ∼10(5)-fold. We also developed a direct screen for protection of acetylcholinesterase from inactivation by nerve agents and used it to isolate variants that degrade the toxic isomer of the coumarin analog and cyclosarin itself with k(cat)/K(M) ∼ 10(7) M(-1) min(-1). We then demonstrated the in vivo prophylactic activity of an evolved variant. These evolved variants and the newly developed screens provide the basis for engineering PON1 for prophylaxis against other G-type agents.
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.