| Autor: |
Hirsch BM; Department of Chemistry, University of Akron, 190 E. Buchtel Commons, Akron, OH 44325, USA., Zheng W |
| Jazyk: |
angličtina |
| Zdroj: |
Molecular bioSystems [Mol Biosyst] 2011 Jan; Vol. 7 (1), pp. 16-28. Date of Electronic Publication: 2010 Sep 15. |
| DOI: |
10.1039/c0mb00033g |
| Abstrakt: |
Silent information regulator 2 (Sir2) enzymes or sirtuins are a family of intracellular protein deacetylases that can catalyze the β-nicotinamide adenine dinucleotide (β-NAD(+))-dependent deacetylation of N(ε)-acetyl-lysine on protein substrates, with the formation of lysine N(ε)-deacetylated protein species and small molecule products, i.e. nicotinamide and 2'-O-acetyl-ADP-ribose (2'-O-AADPR). These enzymes are evolutionarily conserved among all the three kingdoms of life, with the yeast Sir2 being the founding family member. In humans, seven sirtuins, i.e. SIRT1-7, have been identified. The past a few years have witnessed a tremendous interest in investigating the unique mechanism for the sirtuin-catalyzed deacetylation reaction. We have also seen a lot of research employing different strategies to identify different types of the inhibitors for this enzymatic deacetylation reaction. These inhibitors hold great potential toward a fuller exploration of sirtuin biology and pharmacology as well as toward developing novel therapeutics for metabolic and age-related diseases and cancer. Here we would like to review the significant contributions that the judicious use of a variety of N(ε)-acetyl-lysine analogs has been able to make toward our enhanced mechanistic understanding and capability of pharmacological exploitation of the sirtuin-catalyzed deacetylation reaction. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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