Structural and functional characterization of the Vindoline biosynthesis pathway enzymes of Catharanthus roseus
| Autor: | Sudeshna Bose, Saikat Chakrabarti, Harshita Tiwari, Shrabasti Jana, Anindyajit Banerjee, Bilal Ahmad |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Models Molecular Molecular model Catharanthus Vinblastine 01 natural sciences Catalysis Mixed Function Oxygenases Inorganic Chemistry 03 medical and health sciences Apoenzymes Acetyltransferases Catalytic Domain 0103 physical sciences Homology modeling Physical and Theoretical Chemistry Plant Proteins chemistry.chemical_classification 010304 chemical physics biology Chemistry Organic Chemistry Tabersonine Catharanthine Methyltransferases Catharanthus roseus biology.organism_classification Enzyme structure Computer Science Applications Biosynthetic Pathways Molecular Docking Simulation 030104 developmental biology Enzyme Computational Theory and Mathematics Biochemistry Oxygenases Vindoline |
| Zdroj: | Journal of molecular modeling. 24(3) |
| ISSN: | 0948-5023 |
| Popis: | Vinblastine and its related compound vincristine are important mono terpenoid indole alkaloids accumulated in the leaves of Catharanthus roseus (Madagascar periwinkle). They serve as major anticancer drugs. Vinblastine is formed by the condensation of vindoline and catharanthine. The vindoline moiety is derived from tabersonine via vindoline biosynthesis pathway. The reaction sequence from tabersonine to vindoline is now well established and the enzymes involved in this pathway are identified. However, to date, the structures of the enzymes involved in the vindoline biosynthesis pathway are not known, leading to limited mechanistic understanding of the substrate binding and catalysis. The purpose of this work is to provide structural insight regarding all the steps of the vindoline pathway via rigorous homology modeling, molecular docking, and molecular dynamics analyses. Substrate and cofactors required for each step were docked onto the computationally built and validated three-dimensional (3D) model of the corresponding enzyme, and the catalytic reaction was analyzed from the structural point of view. Possible binding modes of the substrates and cofactors were generated and corresponding binding residues were identified. Enzyme-substrate models were verified based on structure evaluation methods and molecular dynamics based approaches. Findings of our analysis would be useful in rational designing of these important enzymes aimed toward bio-production of vindoline. |
| Databáze: | OpenAIRE |
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