Elucidating the Inhibitory Effect of Resveratrol and Its Structural Analogs on Selected Nucleotide-Related Enzymes
Resveratrol, the most widely studied natural phytochemical, has been shown to interact with different target proteins. Previous studies show that resveratrol binds and inhibits DNA polymerases and some other enzymes; however, the binding and functioning mechanisms remain unknown. The elucidated know...
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| Format: | Article |
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MDPI AG
2020-08-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/10/9/1223 |
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| author | Yifei Wu Tze-chen Hsieh Joseph M. Wu Xiaoxiao Wang Joshua S. Christopher Amanda H. Pham Justin David-Li Swaby Lei Lou Zhong-Ru Xie |
| author_facet | Yifei Wu Tze-chen Hsieh Joseph M. Wu Xiaoxiao Wang Joshua S. Christopher Amanda H. Pham Justin David-Li Swaby Lei Lou Zhong-Ru Xie |
| author_sort | Yifei Wu |
| collection | DOAJ |
| description | Resveratrol, the most widely studied natural phytochemical, has been shown to interact with different target proteins. Previous studies show that resveratrol binds and inhibits DNA polymerases and some other enzymes; however, the binding and functioning mechanisms remain unknown. The elucidated knowledge of inhibitory mechanisms of resveratrol will assist us in new drug discovery. We utilized molecular docking and molecular dynamics (MD) simulation to reveal how resveratrol and structurally similar compounds bind to various nucleotide-dependent enzymes, specifically, DNA polymerases, HIV-1 reverse transcriptase, and ribonucleotide reductase. The results show that resveratrol and its analogs exert their inhibitory effects by competing with the substrate dNTPs in these enzymes and blocking elongation of chain polymerization. In addition, the results imply that resveratrol binds to a variety of other ATP-/NTP-binding proteins. |
| first_indexed | 2024-03-10T16:59:23Z |
| format | Article |
| id | doaj.art-e18ac083cafd479da6d32a254e680040 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T16:59:23Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-e18ac083cafd479da6d32a254e6800402023-11-20T11:01:55ZengMDPI AGBiomolecules2218-273X2020-08-01109122310.3390/biom10091223Elucidating the Inhibitory Effect of Resveratrol and Its Structural Analogs on Selected Nucleotide-Related EnzymesYifei Wu0Tze-chen Hsieh1Joseph M. Wu2Xiaoxiao Wang3Joshua S. Christopher4Amanda H. Pham5Justin David-Li Swaby6Lei Lou7Zhong-Ru Xie8Computational Drug Discovery Laboratory, School of Electrical and Computer Engineering, College of Engineering, University of Georgia, Athens, GA 30602, USADepartment of Biochemistry & Molecular Biology, New York Medical College, Valhalla, NY 10595, USADepartment of Biochemistry & Molecular Biology, New York Medical College, Valhalla, NY 10595, USADepartment of Biochemistry & Molecular Biology, New York Medical College, Valhalla, NY 10595, USAComputational Drug Discovery Laboratory, School of Electrical and Computer Engineering, College of Engineering, University of Georgia, Athens, GA 30602, USAComputational Drug Discovery Laboratory, School of Electrical and Computer Engineering, College of Engineering, University of Georgia, Athens, GA 30602, USAComputational Drug Discovery Laboratory, School of Electrical and Computer Engineering, College of Engineering, University of Georgia, Athens, GA 30602, USAComputational Drug Discovery Laboratory, School of Electrical and Computer Engineering, College of Engineering, University of Georgia, Athens, GA 30602, USAComputational Drug Discovery Laboratory, School of Electrical and Computer Engineering, College of Engineering, University of Georgia, Athens, GA 30602, USAResveratrol, the most widely studied natural phytochemical, has been shown to interact with different target proteins. Previous studies show that resveratrol binds and inhibits DNA polymerases and some other enzymes; however, the binding and functioning mechanisms remain unknown. The elucidated knowledge of inhibitory mechanisms of resveratrol will assist us in new drug discovery. We utilized molecular docking and molecular dynamics (MD) simulation to reveal how resveratrol and structurally similar compounds bind to various nucleotide-dependent enzymes, specifically, DNA polymerases, HIV-1 reverse transcriptase, and ribonucleotide reductase. The results show that resveratrol and its analogs exert their inhibitory effects by competing with the substrate dNTPs in these enzymes and blocking elongation of chain polymerization. In addition, the results imply that resveratrol binds to a variety of other ATP-/NTP-binding proteins.https://www.mdpi.com/2218-273X/10/9/1223resveratrolinhibition mechanismnucleotide-related enzymesmolecular dynamics simulationmolecular docking |
| spellingShingle | Yifei Wu Tze-chen Hsieh Joseph M. Wu Xiaoxiao Wang Joshua S. Christopher Amanda H. Pham Justin David-Li Swaby Lei Lou Zhong-Ru Xie Elucidating the Inhibitory Effect of Resveratrol and Its Structural Analogs on Selected Nucleotide-Related Enzymes Biomolecules resveratrol inhibition mechanism nucleotide-related enzymes molecular dynamics simulation molecular docking |
| title | Elucidating the Inhibitory Effect of Resveratrol and Its Structural Analogs on Selected Nucleotide-Related Enzymes |
| title_full | Elucidating the Inhibitory Effect of Resveratrol and Its Structural Analogs on Selected Nucleotide-Related Enzymes |
| title_fullStr | Elucidating the Inhibitory Effect of Resveratrol and Its Structural Analogs on Selected Nucleotide-Related Enzymes |
| title_full_unstemmed | Elucidating the Inhibitory Effect of Resveratrol and Its Structural Analogs on Selected Nucleotide-Related Enzymes |
| title_short | Elucidating the Inhibitory Effect of Resveratrol and Its Structural Analogs on Selected Nucleotide-Related Enzymes |
| title_sort | elucidating the inhibitory effect of resveratrol and its structural analogs on selected nucleotide related enzymes |
| topic | resveratrol inhibition mechanism nucleotide-related enzymes molecular dynamics simulation molecular docking |
| url | https://www.mdpi.com/2218-273X/10/9/1223 |
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