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

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