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The Enzymology of SIR2 Proteins

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Book cover Histone Deacetylases

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

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Abstract

Sir2 enzymes are NAD+-dependent histone/protein deacetylases that tightly couple the cleavage of NAD+ and protein deacetylation to produce nicotinamide, the deacetylated product, and O-acetyl-ADP-ribose. An increasing number of cellular processes including apoptosis, cell cycling, gene silencing, and longevity, have been shown to be dependent and regulated by these deacetylases. Several small molecules have been identified as regulators of Sir2 activity and related cellular processes. Understanding and modulating the cellular activities of these enzymes therefore necessitates an understanding of their enzymology. We review the enzymatic activities, the crystal structures, the basic kinetic mechanism, and the regulation of Sir2 enzymes.

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Borra, M.T., Denu, J.M. (2006). The Enzymology of SIR2 Proteins. In: Verdin, E. (eds) Histone Deacetylases. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1385/1-59745-024-3:219

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