A Molecular Mechanism for Direct Sirtuin Activation by Resveratrol
Figure 2
Crystal structure of human Sirt5 in complex with FdL1-peptide and resveratrol.
A Overall structure of the Sirt5/FdL1/resveratrol complex. Secondary structure elements are labeled as in [42] (elements not present here are in parentheses). B Closer view of the activator binding site, showing the direct interaction between substrate peptide and resveratrol. The 2FO–FC electron density is contoured at 1σ. C Surface representation of the Sirt5 ligand binding sites, showing that the activator closes the peptide channel entrance. The peptide is shown as sticks, the activator as calotte model in orange. D Piceatannol dose response experiments showing the changes in stimulated Sirt5 FdL1 deacetylation activity upon mutation of residues in the resveratrol binding loops. The assignment of symbols to Sirt5 residue replacement mutations, deletions (Δ), or a single residue insertion (R71-P-G72: Pro insertion) is indicated on the right side.