ArticleJournal of the American Chemical Society2019
Biophysical Characterization of a Disabled Double Mutant of Soybean Lipoxygenase: The "Undoing" of Precise Substrate Positioning Relative to Metal Cofactor and an Identified Dynamical Network.
Article in Journal of the American Chemical Society, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- Free energy relationship analysis for temperature dependence of hydride kinetic isotope effects of NADH/NADChemical science · 2026Article
- Computational Method for the Detection of Communication Pathways in Enzymes that Correlate with Experimentally Defined Thermal Activation Networks.The journal of physical chemistry letters · 2026Article
- Correlated Motion-Based Residue Network Analysis Reveals the Distal Thermal Activation in Soybean Lipoxygenase.bioRxiv : the preprint server for biology · 2025Article
- Large Temperature Dependence of Large Kinetic Isotope Effects of Multistep Hydride Reduction ofThe Journal of organic chemistry · 2025Article
- A Foundational Shift in Models for Enzyme Function.Journal of the American Chemical Society · 2025Review
- Structural Effects on the Hydride-Tunneling Kinetic Isotope Effects of NADH/NADThe Journal of organic chemistry · 2025Article
- Understanding the role of oxylipins inFrontiers in plant science · 2025Review
- Substrate Positioning Dynamics Involves a Non-Electrostatic Component to Mediate Catalysis.The journal of physical chemistry letters · 2023Article
- Mutexa: A Computational Ecosystem for Intelligent Protein Engineering.Journal of chemical theory and computation · 2023Review
- Article
- Temporal and spatial resolution of distal protein motions that activate hydrogen tunneling in soybean lipoxygenase.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Dynamical activation of function in metalloenzymes.FEBS letters · 2023Review
- Advances in Hydrogen/Deuterium Exchange Mass Spectrometry and the Pursuit of Challenging Biological Systems.Chemical reviews · 2022Review
- High throughput and quantitative enzymology in the genomic era.Current opinion in structural biology · 2021Review
- Building better polymerases: Engineering the replication of expanded genetic alphabets.The Journal of biological chemistry · 2020Review
- Fatty Acid Allosteric Regulation of C-H Activation in Plant and Animal Lipoxygenases.Molecules (Basel, Switzerland) · 2020Review
- The Soybean Lipoxygenase-Substrate Complex: Correlation between the Properties of Tunneling-Ready States and ENDOR-Detected Structures of Ground States.Biochemistry · 2020Article
- EPR Spectroscopic Studies of Lipoxygenases.Chemistry, an Asian journal · 2020Review
- Comparative kinetic isotope effects on first- and second-order rate constants of soybean lipoxygenase variants uncover a substrate-binding network.The Journal of biological chemistry · 2019Article
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
Abstract
Soybean lipoxygenase (SLO) has served as a prototype for understanding the molecular origin of enzymatic rate accelerations. The double mutant (DM) L546A/L754A is considered a dramatic outlier, due to the unprecedented size and near temperature-independence of its primary kinetic isotope effect, low catalytic efficiency, and elevated enthalpy of activation. To uncover the physical basis of these features, we herein apply three structural probes: hydrogen-deuterium exchange mass spectrometry, room-temperature X-ray crystallography and EPR spectroscopy on four SLO variants (wild-type (WT) enzyme, DM, and the two parental single mutants, L546A and L754A). DM is found to incorporate features of each parent, with the perturbation at position 546 predominantly influencing thermally activated motions that connect the active site to a protein-solvent interface, while mutation at position 754 disrupts the ligand field and solvation near the cofactor iron. However, the expanded active site in DM leads to more active site water molecules and their associated hydrogen bond network, and the individual features from L546A and L754A alone cannot explain the aggregate kinetic properties for DM. Using recently published QM/MM-derived ground-state SLO-substrate complexes for WT and DM, together with the thorough structural analyses presented herein, we propose that the impairment of DM is the combined result of a repositioning of the reactive carbon of linoleic acid substrate with regard to both the iron cofactor and a catalytically linked dynamic region of protein.
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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.