Titlebar

Export bibliographic data
Literature by the same author
plus on the publication server
plus at Google Scholar

 

A molecular mechanism for direct sirtuin activation by resveratrol.

Title data

Gertz, Melanie ; Nguyen, Giang Thi Tuyet ; Fischer, Frank ; Suenkel, Benjamin ; Schlicker, Christine ; Fränzel, Benjamin ; Tomaschewski, Jana ; Aladini, Firouzeh ; Becker, Christian F. W. ; Wolters, Dirk ; Steegborn, Clemens:
A molecular mechanism for direct sirtuin activation by resveratrol.
In: PLoS One. Vol. 7 (2012) Issue 11 . - e49761.
ISSN 1932-6203
DOI: https://doi.org/10.1371/journal.pone.0049761

Abstract in another language

Sirtuins are protein deacetylases regulating metabolism, stress responses, and aging processes, and they were suggested to mediate the lifespan extending effect of a low calorie diet. Sirtuin activation by the polyphenol resveratrol can mimic such lifespan extending effects and alleviate metabolic diseases. The mechanism of Sirtuin stimulation is unknown, hindering the development of improved activators. Here we show that resveratrol inhibits human Sirt3 and stimulates Sirt5, in addition to Sirt1, against fluorophore-labeled peptide substrates but also against peptides and proteins lacking the non-physiological fluorophore modification. We further present crystal structures of Sirt3 and Sirt5 in complex with fluorogenic substrate peptide and modulator. The compound acts as a top cover, closing the Sirtuin's polypeptide binding pocket and influencing details of peptide binding by directly interacting with this substrate. Our results provide a mechanism for the direct activation of Sirtuins by small molecules and suggest that activators have to be tailored to a specific Sirtuin/substrate pair.

Further data

Item Type: Article in a journal
Refereed: Yes
Additional notes: PubMed-ID: 18336301
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: Yes
DDC Subjects: 500 Science > 540 Chemistry
Date Deposited: 17 Apr 2015 10:05
Last Modified: 18 Apr 2018 11:23
URI: https://eref.uni-bayreuth.de/id/eprint/10388