ArticleNature chemical biology2009
Redesigning dehalogenase access tunnels as a strategy for degrading an anthropogenic substrate.
Article in Nature chemical biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 279 citations in OpenAlex.
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- Physics-based modeling in the new era of enzyme engineering.Nature computational science · 2025Review
- Enhancing the stability and catalytic efficiency of alkyl halide dehalogenase through poloxamer temperature-sensitive gel.PloS one · 2025Article
- Mining unique cysteine synthetases and computational study on thoroughly eliminating feedback inhibition through tunnel engineering.Protein science : a publication of the Protein Society · 2024Article
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- Engineering Enzymes for Environmental Sustainability.Angewandte Chemie (International ed. in English) · 2023Review
- Engineering Enzymes for Environmental Sustainability.Angewandte Chemie (Weinheim an der Bergstrasse, Germany) · 2023Review
- Multimeric structure of a subfamily III haloalkane dehalogenase-like enzyme solved by combination of cryo-EM and x-ray crystallography.Protein science : a publication of the Protein Society · 2023Article
- Fishing for Catalysis: Experimental Approaches to Narrowing Search Space in Directed Evolution of Enzymes.JACS Au · 2023Review
- Structure-guided engineering of a flavin-containing monooxygenase for the efficient production of indirubin.Bioresources and bioprocessing · 2022Article
- Structure-guided steric hindrance engineering of Bacillus badius phenylalanine dehydrogenase for efficient L-homophenylalanine synthesis.Biotechnology for biofuels · 2021Article
- Recent advances in user-friendly computational tools to engineer protein function.Briefings in bioinformatics · 2021Review
- Biocatalytic approaches for the synthesis of optically pure vic-halohydrins.Applied microbiology and biotechnology · 2021Review
- Tunnel engineering for modulating the substrate preference in cytochrome P450Bioresources and bioprocessing · 2021Article
- Stabilizing AqdC, a Pseudomonas Quinolone Signal-Cleaving Dioxygenase from Mycobacteria, by FRESCO-Based Protein Engineering.Chembiochem : a European journal of chemical biology · 2021Article
15 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Engineering enzymes to degrade anthropogenic compounds efficiently is challenging. We obtained Rhodococcus rhodochrous haloalkane dehalogenase mutants with up to 32-fold higher activity than wild type toward the toxic, recalcitrant anthropogenic compound 1,2,3-trichloropropane (TCP) using a new strategy. We identified key residues in access tunnels connecting the buried active site with bulk solvent by rational design and randomized them by directed evolution. The most active mutant has large aromatic residues at two out of three randomized positions and two positions modified by site-directed mutagenesis. These changes apparently enhance activity with TCP by decreasing accessibility of the active site for water molecules, thereby promoting activated complex formation. Kinetic analyses confirmed that the mutations improved carbon-halogen bond cleavage and shifted the rate-limiting step to the release of products. Engineering access tunnels by combining computer-assisted protein design with directed evolution may be a valuable strategy for refining catalytic properties of enzymes with buried active sites.
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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.