Elucidating the Inhibitory Effect of Resveratrol and Its Structural Analogs on Selected Nucleotide-Related Enzymes
| Autor: | Justin David-Li Swaby, Joseph M. Wu, Lei Lou, Zhong-Ru Xie, Tze-chen Hsieh, Xiaoxiao Wang, Amanda H. Pham, Yifei Wu, Joshua S. Christopher |
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| Rok vydání: | 2020 |
| Předmět: |
endocrine system diseases
Protein Conformation DNA polymerase lcsh:QR1-502 resveratrol Resveratrol Ligands Biochemistry lcsh:Microbiology chemistry.chemical_compound 0302 clinical medicine Catalytic Domain Drug Discovery Nucleotide Enzyme Inhibitors skin and connective tissue diseases chemistry.chemical_classification 0303 health sciences Molecular Structure biology Drug discovery food and beverages HIV Reverse Transcriptase Molecular Docking Simulation molecular dynamics simulation Ribonucleotide reductase 030220 oncology & carcinogenesis inhibition mechanism hormones hormone substitutes and hormone antagonists In Vitro Techniques Inhibitory postsynaptic potential Binding Competitive Article Structure-Activity Relationship 03 medical and health sciences Ribonucleotide Reductases Humans Molecular Biology DNA Polymerase III 030304 developmental biology organic chemicals Hydrogen Bonding molecular docking DNA Polymerase I Reverse transcriptase Enzyme chemistry biology.protein nucleotide-related enzymes |
| Zdroj: | Biomolecules, Vol 10, Iss 1223, p 1223 (2020) Biomolecules Volume 10 Issue 9 |
| ISSN: | 2218-273X |
| DOI: | 10.3390/biom10091223 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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