Structural analysis of the inhibitory effects of polyphenols, (+)‐hopeaphenol and (−)‐isohopeaphenol, on human SIRT1

• Published in: BioFactors (Oxford) 2019-03, Vol.45 (2), p.253-258
• Main Authors: Loisruangsin, Arthorn, Hikita, Kiyomi, Seto, Norikazu, Niwa, Masatake, Takaya, Yoshiaki, Kaneda, Norio
• Format: Article
• Language: English
• Subjects: (+)‐hopeaphenol; (−)‐isohopeaphenol; human SIRT1; Humans; MD simulation; molecular docking; Phenols - chemistry; Phenols - pharmacology; Polyphenols - chemistry; Polyphenols - pharmacology; Protein Binding; Resveratrol - chemistry; Resveratrol - pharmacology; resveratrol tetramer; Sirtuin 1 - antagonists & inhibitors; Sirtuin 1 - chemistry; Sirtuin 1 - metabolism; Stilbenes - chemistry; Stilbenes - pharmacology
• ISSN: 0951-6433; 1872-8081
• DOI: 10.1002/biof.1479

Human sirtuin 1 (hSIRT1) is a NAD+‐dependent deacetylase that regulates several cellular processes. Unlike resveratrol, natural polymeric phenolic compounds isolated from Vitaceae are mostly hSIRT1 inhibitors. The resveratrol tetramer, (+)‐hopeaphenol ((+)‐HP), and its geometric isomer, (−)‐isohopeaphenol ((−)‐iHP), were tested for inhibitory effects on purified hSIRT1 using a fluorescent derivative of peptide substrate p53‐AMC (Fluor de Lys) and a cofactor NAD+. The Lineweaver–Burk plots indicated that both (+)‐HP and (−)‐iHP were competitive inhibitors against NAD+. Computer‐assisted modeling of the binding of these molecules with hSIRT1 protein provided the most feasible conformation of the enzyme–inhibitor complex. © 2018 BioFactors, 45(2):253–258, 2019