Crystal Structure Gives Insights into Sirtuin Function

Researchers have unveiled the high-resolution crystal structure of a yeast Sir2 sirtuin enzyme that helps to explain how it functions metabolically and how it participates in many vital processes including metabolism, aging, and gene expression.

The crystal structure of Sir2, which was revealed in the November 2003 issue of Structure, was determined while the enzyme was interacting with two other molecules. One site on the enzyme was bound to a derivative of a molecule called NAD, while a second site was bound to a specific site on a histone protein.

"The sirtuins, whether we find them in bacteria, yeast, or humans, all rely on another molecule called NAD, required primarily for metabolism, to do their jobs,” explained senior author Dr. Ronen Marmorstein, a professor at the Wistar Institute (Philadelphia, PA, USA). "There is only so much NAD available at any given time, however, and if it is being used by the enzymes involved in metabolic processes, it may not be available to the sirtuins whose job it is to shut down unnecessary gene expression. The resulting unchecked genetic activity would expend needless energy, promote the production of genetic abnormalities, and may well be implicated in the aging process.”





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