at Google ScholarTitle data
You, Weijie ; Rotili, Dante ; Li, Tie-Mei ; Kambach, Christian ; Meleshin, Marat ; Schutkowski, Mike ; Chua, Katrin F. ; Mai, Antonello ; Steegborn, Clemens:
Structural Basis of Sirtuin 6 Activation by Synthetic Small Molecules.
In: Angewandte Chemie International Edition.
Vol. 56
(2017)
Issue 4
.
- pp. 1007-1011.
ISSN 1521-3773
DOI: https://doi.org/10.1002/anie.201610082
Abstract in another language
Sirtuins are protein deacylases regulating metabolism and stress responses, and are implicated in aging-related diseases. Small molecule activators for the human sirtuins Sirt1-7 are sought as chemical tools and potential therapeutics, such as for cancer. Activators are available for Sirt1 and exploit its unique N-terminus, whereas drug-like activators for Sirt2-7 are lacking. We synthesized and screened pyrrolo[1,2-a]quinoxaline derivatives, yielding the first synthetic Sirt6 activators. Biochemical assays show direct, substrate-independent compound binding to the Sirt6 catalytic core and potent activation of Sirt6-dependent deacetylation of peptide substrates and complete nucleosomes. Crystal structures of Sirt6/activator complexes reveal that the compounds bind to a Sirt6-specific acyl channel pocket and identify key interactions. Our results establish potent Sirt6 activation with small molecules and provide a structural basis for further development of Sirt6 activators as tools and therapeutics.
Further data
| Item Type: | Article in a journal |
|---|---|
| Refereed: | Yes |
| Institutions of the University: | Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Chair Biochemistry > Chair Biochemistry - Univ.-Prof. Dr. Clemens Steegborn Faculties Faculties > Faculty of Biology, Chemistry and Earth Sciences Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Chair Biochemistry |
| Result of work at the UBT: | No |
| DDC Subjects: | 600 Technology, medicine, applied sciences |
| Date Deposited: | 06 Apr 2017 08:33 |
| Last Modified: | 02 Nov 2023 14:11 |
| URI: | https://eref.uni-bayreuth.de/id/eprint/36701 |