ArticleJournal of the American Chemical Society2013
Molecular engineering of organophosphate hydrolysis activity from a weak promiscuous lactonase template.
Article in Journal of the American Chemical Society, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 59 citations in OpenAlex.
- Bioinspired Framework Catalysts: From Enzyme Immobilization to Biomimetic Catalysis.Chemical reviews · 2023Review
- Ultrahigh-Throughput Directed Evolution of a Metal-Free α/β-Hydrolase with a Cys-His-Asp Triad into an Efficient Phosphotriesterase.Journal of the American Chemical Society · 2023Article
- Organophosphorus Nerve Agents: Types, Toxicity, and Treatments.Journal of toxicology · 2020Review
- Evolutionary repurposing of a sulfatase: A new Michaelis complex leads to efficient transition state charge offset.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Rational engineering of a native hyperthermostable lactonase into a broad spectrum phosphotriesterase.Scientific reports · 2017Article
- Organophosphate-Hydrolyzing Enzymes as First-Line of Defence Against Nerve Agent-Poisoning: Perspectives and the Road Ahead.The protein journal · 2016Review
- Functional Trade-Offs in Promiscuous Enzymes Cannot Be Explained by Intrinsic Mutational Robustness of the Native Activity.PLoS genetics · 2016Article
- How mutational epistasis impairs predictability in protein evolution and design.Protein science : a publication of the Protein Society · 2016Article
- Function discovery and structural characterization of a methylphosphonate esterase.Biochemistry · 2015Article
- Expanding the enzyme universe: accessing non-natural reactions by mechanism-guided directed evolution.Angewandte Chemie (International ed. in English) · 2015Review
- Active site loop conformation regulates promiscuous activity in a lactonase from Geobacillus kaustophilus HTA426.PloS one · 2015Article
- Article
- SacPox from the thermoacidophilic crenarchaeon Sulfolobus acidocaldarius is a proficient lactonase.BMC research notes · 2014Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Rapid evolution of enzymes provides unique molecular insights into the remarkable adaptability of proteins and helps to elucidate the relationship between amino acid sequence, structure, and function. We interrogated the evolution of the phosphotriesterase from Pseudomonas diminuta (PdPTE), which hydrolyzes synthetic organophosphates with remarkable catalytic efficiency. PTE is thought to be an evolutionarily "young" enzyme, and it has been postulated that it has evolved from members of the phosphotriesterase-like lactonase (PLL) family that show promiscuous organophosphate-degrading activity. Starting from a weakly promiscuous PLL scaffold (Dr0930 from Deinococcus radiodurans ), we designed an extremely efficient organophosphate hydrolase (OPH) with broad substrate specificity using rational and random mutagenesis in combination with in vitro activity screening. The OPH activity for seven organophosphate substrates was simultaneously enhanced by up to 5 orders of magnitude, achieving absolute values of catalytic efficiencies up to 10(6) M(-1) s(-1). Structural and computational analyses identified the molecular basis for the enhanced OPH activity of the engineered PLL variants and demonstrated that OPH catalysis in PdPTE and the engineered PLL differ significantly in the mode of substrate binding.
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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.