ArticleRSC chemical biology2021
Substrate inhibition by the blockage of product release and its control by tunnel engineering.
Article in RSC chemical biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed.
- Molecular Access Engineering for Microbial Biocatalysis: from Enzyme Tunnels to Microbial Cell Factories.Journal of microbiology and biotechnology · 2026Review
- Degradation of Sulfadiazine by Biogenic Manganese Oxides Coupled with Syringaldehyde: Performance, Mechanism, Toxicity, and Environmental Applicability.Molecules (Basel, Switzerland) · 2026Article
- Engineering of Corynebacterium glutamicum for biosynthesis of the pharmaceutically active N-acetyltyramine: establishing and optimizing de novo production.Journal of biological engineering · 2026Article
- Trichodiene: a committed intermediate and a chink in the armor of mycotoxigenicApplied and environmental microbiology · 2026Article
- Fungal cellulases: a comprehensive review on production, innovations, and applications.Archives of microbiology · 2026Review
- Combination of enzyme engineering and quorum sensing system for efficient de novo biosynthesis of β-arbutin inSynthetic and systems biotechnology · 2026Article
- Efficient synthesis of l-DOPA inSynthetic and systems biotechnology · 2026Article
- Current Progress and Future Directions of Enzyme Technology in Food Nutrition: A Comprehensive Review of Processing, Nutrition, and Functional Innovation.Foods (Basel, Switzerland) · 2026Review
- Thiazole substitution of a labile amide bond-a new option toward antiplasmodial pantothenamide-mimics.Antimicrobial agents and chemotherapy · 2025Article
- Personalized Genotype-Based Approach for Treatment of Phenylketonuria.Journal of inherited metabolic disease · 2025Article
- Article
- β-Carotene alleviates substrate inhibition caused by asymmetric cooperativity.Nature communications · 2025Article
- Enhancing β-Galactosidase Performance for Galactooligosaccharides Preparation via Strategic Glucose Re-Tunneling.International journal of molecular sciences · 2024Article
- Mining unique cysteine synthetases and computational study on thoroughly eliminating feedback inhibition through tunnel engineering.Protein science : a publication of the Protein Society · 2024Article
- Analysis of phosphofructokinase-1 activity as affected by pH and ATP concentration.Scientific reports · 2024Article
- Optimization, gene cloning, expression, and molecular docking insights for enhanced cellulase enzyme production by Bacillus amyloliquefaciens strain elh1.Microbial cell factories · 2024Article
- Understanding the stability of a plastic-degrading Rieske iron oxidoreductase system.Protein science : a publication of the Protein Society · 2024Article
- Optimized decolorization of two poly azo dyes Sirius Red and Sirius Blue using laccase-mediator system.3 Biotech · 2024Article
- Impact of Acetic Acid Supplementation in Polyhydroxyalkanoates Production by Cupriavidus necator Using Mixture-Process Design and Artificial Neural Network.Applied biochemistry and biotechnology · 2024Article
- Synthesis, Optimization, and Characterization of Cellulase Enzyme Obtained from ThermotolerantJournal of microbiology and biotechnology · 2024Article
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Substrate inhibition is the most common deviation from Michaelis-Menten kinetics, occurring in approximately 25% of known enzymes. It is generally attributed to the formation of an unproductive enzyme-substrate complex after the simultaneous binding of two or more substrate molecules to the active site. Here, we show that a single point mutation (L177W) in the haloalkane dehalogenase LinB causes strong substrate inhibition. Surprisingly, a global kinetic analysis suggested that this inhibition is caused by binding of the substrate to the enzyme-product complex. Molecular dynamics simulations clarified the details of this unusual mechanism of substrate inhibition: Markov state models indicated that the substrate prevents the exit of the halide product by direct blockage and/or restricting conformational flexibility. The contributions of three residues forming the possible substrate inhibition site (W140A, F143L and I211L) to the observed inhibition were studied by mutagenesis. An unusual synergy giving rise to high catalytic efficiency and reduced substrate inhibition was observed between residues L177W and I211L, which are located in different access tunnels of the protein. These results show that substrate inhibition can be caused by substrate binding to the enzyme-product complex and can be controlled rationally by targeted amino acid substitutions in enzyme access tunnels.
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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.