The Reaction Mechanism of Loganic Acid Methyltransferase: A Molecular Dynamics Simulation and Quantum Mechanics Study
In this work, the catalytic mechanism of loganic acid methyltransferase was characterized at the molecular level. This enzyme is responsible for the biosynthesis of loganin, which is a precursor for a wide range of biologically active compounds. Due to the lack of detailed knowledge about this proce...
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| Format: | Article |
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MDPI AG
2023-07-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/15/5767 |
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| author | Mateusz Jędrzejewski Łukasz Szeleszczuk Dariusz Maciej Pisklak |
| author_facet | Mateusz Jędrzejewski Łukasz Szeleszczuk Dariusz Maciej Pisklak |
| author_sort | Mateusz Jędrzejewski |
| collection | DOAJ |
| description | In this work, the catalytic mechanism of loganic acid methyltransferase was characterized at the molecular level. This enzyme is responsible for the biosynthesis of loganin, which is a precursor for a wide range of biologically active compounds. Due to the lack of detailed knowledge about this process, the aim of this study was the analysis of the structure and activity of loganic acid methyltransferase. Using molecular dynamics (MD) simulations, the native structure of the complex was reconstructed, and the key interactions between the substrate and loganic acid methyltransferase were investigated. Subsequently, the structures obtained from the simulations were used for quantum chemical (QM) calculations. The QM calculations allowed for the exploration of the energetic aspects of the reaction and the characterization of its mechanism. The results obtained in this study suggest the existence of two patterns of interactions between loganic acid methyltransferase and the substrate. The role of residue Q38 in the binding and orientation of the substrate’s carboxyl group was also demonstrated. By employing a combined MD and QM approach, the experimental reaction barrier was reproduced, and detailed insights into the enzymatic activity mechanism of loganic acid methyltransferase were revealed. |
| first_indexed | 2024-03-11T00:20:40Z |
| format | Article |
| id | doaj.art-8c9ff26c6a284bd5acc3a0f177bc5c8f |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-11T00:20:40Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-8c9ff26c6a284bd5acc3a0f177bc5c8f2023-11-18T23:18:37ZengMDPI AGMolecules1420-30492023-07-012815576710.3390/molecules28155767The Reaction Mechanism of Loganic Acid Methyltransferase: A Molecular Dynamics Simulation and Quantum Mechanics StudyMateusz Jędrzejewski0Łukasz Szeleszczuk1Dariusz Maciej Pisklak2Department of Organic and Physical Chemistry, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1, 02-093 Warsaw, PolandDepartment of Organic and Physical Chemistry, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1, 02-093 Warsaw, PolandDepartment of Organic and Physical Chemistry, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1, 02-093 Warsaw, PolandIn this work, the catalytic mechanism of loganic acid methyltransferase was characterized at the molecular level. This enzyme is responsible for the biosynthesis of loganin, which is a precursor for a wide range of biologically active compounds. Due to the lack of detailed knowledge about this process, the aim of this study was the analysis of the structure and activity of loganic acid methyltransferase. Using molecular dynamics (MD) simulations, the native structure of the complex was reconstructed, and the key interactions between the substrate and loganic acid methyltransferase were investigated. Subsequently, the structures obtained from the simulations were used for quantum chemical (QM) calculations. The QM calculations allowed for the exploration of the energetic aspects of the reaction and the characterization of its mechanism. The results obtained in this study suggest the existence of two patterns of interactions between loganic acid methyltransferase and the substrate. The role of residue Q38 in the binding and orientation of the substrate’s carboxyl group was also demonstrated. By employing a combined MD and QM approach, the experimental reaction barrier was reproduced, and detailed insights into the enzymatic activity mechanism of loganic acid methyltransferase were revealed.https://www.mdpi.com/1420-3049/28/15/5767methyltransferasemolecular dynamicsquantum chemical cluster approachreaction mechanismsenzymatic catalysis |
| spellingShingle | Mateusz Jędrzejewski Łukasz Szeleszczuk Dariusz Maciej Pisklak The Reaction Mechanism of Loganic Acid Methyltransferase: A Molecular Dynamics Simulation and Quantum Mechanics Study Molecules methyltransferase molecular dynamics quantum chemical cluster approach reaction mechanisms enzymatic catalysis |
| title | The Reaction Mechanism of Loganic Acid Methyltransferase: A Molecular Dynamics Simulation and Quantum Mechanics Study |
| title_full | The Reaction Mechanism of Loganic Acid Methyltransferase: A Molecular Dynamics Simulation and Quantum Mechanics Study |
| title_fullStr | The Reaction Mechanism of Loganic Acid Methyltransferase: A Molecular Dynamics Simulation and Quantum Mechanics Study |
| title_full_unstemmed | The Reaction Mechanism of Loganic Acid Methyltransferase: A Molecular Dynamics Simulation and Quantum Mechanics Study |
| title_short | The Reaction Mechanism of Loganic Acid Methyltransferase: A Molecular Dynamics Simulation and Quantum Mechanics Study |
| title_sort | reaction mechanism of loganic acid methyltransferase a molecular dynamics simulation and quantum mechanics study |
| topic | methyltransferase molecular dynamics quantum chemical cluster approach reaction mechanisms enzymatic catalysis |
| url | https://www.mdpi.com/1420-3049/28/15/5767 |
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