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Catalysis and mechanistic insights into sirtuin activation. 2011

Kristin E Dittenhafer-Reed, and Jessica L Feldman, and John M Denu
Department of Biomolecular Chemistry, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53706, USA.

SIRT1 is a member of the Sir2 family of NAD(+)-dependent protein deacetylases. The central role of SIRT1 in multiple metabolic and age-related pathways has pushed SIRT1 to the forefront to discover small-molecule activators. Promising compounds, including resveratrol and SRT1720 have been reported, however, whether these compounds are direct activators and the mechanism by which they activate remains poorly defined. This review examines the current debate surrounding purported activators, and will focus on the assays used in screening compounds, sirtuin catalysis, and the mechanistic basis for their actions. We discuss the potential pathways of SIRT1 activation that could be exploited for the development of novel therapeutics for treating type II diabetes, neurodegeneration, and diseases associated with aging.

UI MeSH Term Description Entries
D011487 Protein Conformation The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). Conformation, Protein,Conformations, Protein,Protein Conformations
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D055162 Biocatalysis The facilitation of biochemical reactions with the aid of naturally occurring catalysts such as ENZYMES.
D056564 Sirtuin 1 A sirtuin family member found primarily in the CELL NUCLEUS. It is an NAD-dependent deacetylase with specificity towards HISTONES and a variety of proteins involved in gene regulation. Silent Mating Type Information Regulation 2 Homolog 1,Sirt1

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