| First Author | Hubbard BP | Year | 2013 |
| Journal | Science | Volume | 339 |
| Issue | 6124 | Pages | 1216-9 |
| PubMed ID | 23471411 | Mgi Jnum | J:194036 |
| Mgi Id | MGI:5470182 | Doi | 10.1126/science.1231097 |
| Citation | Hubbard BP, et al. (2013) Evidence for a common mechanism of SIRT1 regulation by allosteric activators. Science 339(6124):1216-9 |
| abstractText | A molecule that treats multiple age-related diseases would have a major impact on global health and economics. The SIRT1 deacetylase has drawn attention in this regard as a target for drug design. Yet controversy exists around the mechanism of sirtuin-activating compounds (STACs). We found that specific hydrophobic motifs found in SIRT1 substrates such as PGC-1alpha and FOXO3a facilitate SIRT1 activation by STACs. A single amino acid in SIRT1, Glu(230), located in a structured N-terminal domain, was critical for activation by all previously reported STAC scaffolds and a new class of chemically distinct activators. In primary cells reconstituted with activation-defective SIRT1, the metabolic effects of STACs were blocked. Thus, SIRT1 can be directly activated through an allosteric mechanism common to chemically diverse STACs. |
