Publication Date

Fall 2023

Degree Type


Degree Name

Master of Science (MS)




Ningkun Wang; Nicholas Esker; Emma Carroll


SIRT1 is an NAD+-dependent lysine deacetylase that is involved in many important cellular pathways. The protein has an extended N-terminal domain that seems to play a role in regulating its activity. Sirtuin Activating Compounds (STACs) are allosteric activators, such as resveratrol, that regulate the activity of SIRT1. STACs bind to the N-terminal STAC Binding Domain (SBD) in SIRT1. Past literature has found that SIRT1 activity can be increased, decreased, or remain unchanged by resveratrol depending on the identity of the peptide substrate. The goal of this study is to clarify the mechanism for substrate-specific allosteric regulation by resveratrol. The interactions between resveratrol and SIRT1 remain poorly understood from a quantitative perspective. Our lab has found that resveratrol changes the enzyme activity of SIRT1 by altering its substrate recognition for different peptide substrates. Additionally, we hypothesize that the conformational changes that SIRT1 experiences upon binding to various substrates alter the way resveratrol interacts with the SIRT1•substrate complex. In turn, resveratrol may then affect SIRT1 conformation and stability in a substrate-specific manner. To this end, this study uses fluorescence-based binding assays to quantify the KD values for the SIRT1•resveratrol binding interactions in the presence of various substrates. We are also using small angle X-ray scattering (SAXS) and differential scanning fluorimetry (DSF) to determine resveratrol’s effects on SIRT1 conformation and stability.

Included in

Chemistry Commons