Elucidating the Inhibitory Effect of Resveratrol and Its Structural Analogs on Selected Nucleotide-Related Enzymes

• Published in: Biomolecules (Basel, Switzerland) Vol. 10; no. 9; p. 1223
• Main Authors: Wu, Yifei, Hsieh, Tze-Chen, Wu, Joseph M, Wang, Xiaoxiao, Christopher, Joshua S, Pham, Amanda H, Swaby, Justin David-Li, Lou, Lei, Xie, Zhong-Ru
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 22.08.2020; MDPI
• Subjects: Adenosine triphosphate; Binding sites; Deoxyribonucleic acid; DNA; DNA polymerase; DNA-directed DNA polymerase; Enzyme kinetics; Enzymes; HIV; Human immunodeficiency virus; inhibition mechanism; Kinases; Ligands; molecular docking; Molecular dynamics; molecular dynamics simulation; Nucleotide analogs; nucleotide-related enzymes; Proteins; Resveratrol; Ribonucleotide reductase; RNA polymerase; RNA-directed DNA polymerase; inhibition mechanism; molecular docking; resveratrol; nucleotide-related enzymes; molecular dynamics simulation
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom10091223

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.