Structural analysis of the inhibitory effects of polyphenols, (+)‐hopeaphenol and (−)‐isohopeaphenol, on human SIRT1. (11th December 2018)

• Record Type: Journal Article
• Authors: Loisruangsin, Arthorn; Hikita, Kiyomi; Seto, Norikazu; Niwa, Masatake; Takaya, Yoshiaki; Kaneda, Norio
• Is Part Of: BioFactors. Volume 45:Number 2(2019)
• Page Start: 253
• Page End: 258
• Publication Date: 2018-12-11
• Subjects: human SIRT1 -- (−)‐isohopeaphenol -- (+)‐hopeaphenol -- resveratrol tetramer -- molecular docking -- MD simulation; Vitamins -- Physiological effect -- Periodicals; Trace elements -- Physiological effect -- Periodicals; Growth factors -- Physiological effect -- Periodicals; Plant growth promoting substances -- Physiological effect -- Periodicals; Biochemistry -- Periodicals; Nutritional Physiological Phenomena -- Periodicals; Trace Elements -- metabolism -- Periodicals; Vitamins -- metabolism -- Periodicals; Molecular Biology -- Periodicals; 612.399
• DOI: 10.1002/biof.1479
• Languages: English
• ISSNs: 0951-6433

Abstract

Abstract: 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