While many factors affect lifespan and healthspan, in recent years there has been a significant correlation between Sirtuin proteins and longevity, specifically Sirtuin 6. Sirtuin 6, or SIRT6, is an NAD+ dependent protein deacetylase. Recent literature has shown that the overexpression of SIRT6 lengthened the lifespan of mice by 23%, while also maintaining their healthspan. In addition to the catalytic pocket, SIRT6, like many other proteins, contains a zinc finger, a structural motif on the Sirtuin. While little is currently known about the function of the zinc finger on SIRT6, it may play a crucial role in the proper folding of the protein despite its large distance from the catalytic site of SIRT6. This research attempts to analyze and explore the potential allosteric effects of the zinc finger via thermal analysis and activity assays. Through various molecular manipulations of the SIRT6 zinc finger it is evident that it plays a critical role in the function of the protein. As SIRT6 is a protein with a strong connection to a lengthened lifespan, the analysis of its zinc finger as well as the overall structure can contribute to further breakthroughs in the study of human aging.

Exploring the allosteric effects of the SIRT6 zinc finger

ACS Spring 2022

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