Laccase from <i>Melanocarpus albomyces</i>: Molecular Docking Analysis with First-Generation Tetracyclines Through a Mechanistic Approach
Laccases are versatile enzymes capable of oxidizing a wide variety of antibiotics. In this study, the mechanism of catalytic oxidation of first-generation tetracyclines, namely, oxytetracycline, tetracycline, and chlortetracycline, by the <i>Melanocarpus albomyces</i> laccase enzyme was...
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2025-05-01
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| author | José Muñoz-Espinoza Germán Barriga-González Gino Corsini Sebastián Lagos Andrés Barriga González Nadia Gavilán de Fátima |
| author_facet | José Muñoz-Espinoza Germán Barriga-González Gino Corsini Sebastián Lagos Andrés Barriga González Nadia Gavilán de Fátima |
| author_sort | José Muñoz-Espinoza |
| collection | DOAJ |
| description | Laccases are versatile enzymes capable of oxidizing a wide variety of antibiotics. In this study, the mechanism of catalytic oxidation of first-generation tetracyclines, namely, oxytetracycline, tetracycline, and chlortetracycline, by the <i>Melanocarpus albomyces</i> laccase enzyme was investigated using molecular docking and DFT calculations. Molecular docking studies revealed that all three substrates exhibit negative interaction energies, indicating stable enzyme–substrate complexes, with tetracycline and chlortetracycline showing the highest binding affinities. Global reactivity indices obtained by DFT confirmed the high electrophilicity of the enzyme active site, particularly the aminoacidic residues Glu235 and His508, favoring electron transfer from the substrates. In addition, NBO analysis allowed quantification of the energy of hydrogen bonds in enzyme–substrate interactions, evidencing their key role in the stabilization of the complex. Proton transfer analysis suggested two possible mechanisms: (1) a direct concerted transfer and (2) a process mediated by water molecules. The results provide insights into the thermodynamics, electronic structure, and nature of intermolecular interactions governing the oxidation of tetracyclines by the enzyme, highlighting their potential in bioremediation strategies for antibiotic degradation. |
| format | Article |
| id | doaj-art-e54b69f37bab45afb8ba19d264eef6ac |
| institution | Kabale University |
| issn | 2673-6918 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
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| series | Compounds |
| spelling | doaj-art-e54b69f37bab45afb8ba19d264eef6ac2025-08-20T03:26:56ZengMDPI AGCompounds2673-69182025-05-01521710.3390/compounds5020017Laccase from <i>Melanocarpus albomyces</i>: Molecular Docking Analysis with First-Generation Tetracyclines Through a Mechanistic ApproachJosé Muñoz-Espinoza0Germán Barriga-González1Gino Corsini2Sebastián Lagos3Andrés Barriga González4Nadia Gavilán de Fátima5Laboratorio de Química Teórica, Departamento de Química, Facultad de Ciencias, Universidad de Chile, Santiago 7800003, ChileLaboratorio MACEDONIA, Departamento de Química, Universidad Metropolitana de Ciencias de la Educación, Santiago 7760197, ChileLaboratorio de Microbiología Molecular y Compuestos Bioactivos, Instituto de Ciencias Biomédicas, Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Santiago 8320000, ChileLaboratorio de Microbiología Molecular y Compuestos Bioactivos, Instituto de Ciencias Biomédicas, Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Santiago 8320000, ChileUnidad de Espectrometría de Masas-CEPEDEQ, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago 8320000, ChileLaboratorio de Microbiología Molecular y Compuestos Bioactivos, Instituto de Ciencias Biomédicas, Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Santiago 8320000, ChileLaccases are versatile enzymes capable of oxidizing a wide variety of antibiotics. In this study, the mechanism of catalytic oxidation of first-generation tetracyclines, namely, oxytetracycline, tetracycline, and chlortetracycline, by the <i>Melanocarpus albomyces</i> laccase enzyme was investigated using molecular docking and DFT calculations. Molecular docking studies revealed that all three substrates exhibit negative interaction energies, indicating stable enzyme–substrate complexes, with tetracycline and chlortetracycline showing the highest binding affinities. Global reactivity indices obtained by DFT confirmed the high electrophilicity of the enzyme active site, particularly the aminoacidic residues Glu235 and His508, favoring electron transfer from the substrates. In addition, NBO analysis allowed quantification of the energy of hydrogen bonds in enzyme–substrate interactions, evidencing their key role in the stabilization of the complex. Proton transfer analysis suggested two possible mechanisms: (1) a direct concerted transfer and (2) a process mediated by water molecules. The results provide insights into the thermodynamics, electronic structure, and nature of intermolecular interactions governing the oxidation of tetracyclines by the enzyme, highlighting their potential in bioremediation strategies for antibiotic degradation.https://www.mdpi.com/2673-6918/5/2/17<i>Melanocarpus albomyces</i> laccasemolecular dockingtetracyclines |
| spellingShingle | José Muñoz-Espinoza Germán Barriga-González Gino Corsini Sebastián Lagos Andrés Barriga González Nadia Gavilán de Fátima Laccase from <i>Melanocarpus albomyces</i>: Molecular Docking Analysis with First-Generation Tetracyclines Through a Mechanistic Approach Compounds <i>Melanocarpus albomyces</i> laccase molecular docking tetracyclines |
| title | Laccase from <i>Melanocarpus albomyces</i>: Molecular Docking Analysis with First-Generation Tetracyclines Through a Mechanistic Approach |
| title_full | Laccase from <i>Melanocarpus albomyces</i>: Molecular Docking Analysis with First-Generation Tetracyclines Through a Mechanistic Approach |
| title_fullStr | Laccase from <i>Melanocarpus albomyces</i>: Molecular Docking Analysis with First-Generation Tetracyclines Through a Mechanistic Approach |
| title_full_unstemmed | Laccase from <i>Melanocarpus albomyces</i>: Molecular Docking Analysis with First-Generation Tetracyclines Through a Mechanistic Approach |
| title_short | Laccase from <i>Melanocarpus albomyces</i>: Molecular Docking Analysis with First-Generation Tetracyclines Through a Mechanistic Approach |
| title_sort | laccase from i melanocarpus albomyces i molecular docking analysis with first generation tetracyclines through a mechanistic approach |
| topic | <i>Melanocarpus albomyces</i> laccase molecular docking tetracyclines |
| url | https://www.mdpi.com/2673-6918/5/2/17 |
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