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Crystal structures of Sirt3 complexes with 4'-bromo-resveratrol reveal binding sites and inhibition mechanism.

Title data

Nguyen, Giang Thi Tuyet ; Gertz, Melanie ; Steegborn, Clemens:
Crystal structures of Sirt3 complexes with 4'-bromo-resveratrol reveal binding sites and inhibition mechanism.
In: Chemistry & Biology. Vol. 20 (21 November 2013) Issue 11 . - pp. 1375-1385.
ISSN 1879-1301
DOI: https://doi.org/10.1016/j.chembiol.2013.09.019

Abstract in another language

Sirtuins are protein deacetylases regulating aging processes and various physiological functions. Resveratrol, a polyphenol found in red wine, activates human Sirt1 and inhibits Sirt3, and it can mimic calorie restriction effects, such as lifespan extension in lower organisms. The mechanism of Sirtuin modulation by resveratrol is not well understood. We used 4'-bromo-resveratrol (5-(2-(4-hydroxyphenyl)vinyl)-1,3-benzenediol) to study Sirt1 and Sirt3 modulation. Despite its similarity to the Sirt1 activator resveratrol, the compound potently inhibited both, Sirt1 and Sirt3. Crystal structures of Sirt3 in complex with a fluorophore-labeled and with a native substrate peptide, respectively, in presence of 4'-bromo-resveratrol reveal two compound binding sites. Biochemical studies identify the internal site and substrate competition as the mechanism for inhibition, providing a drug target site, and homology modeling suggests that the second, allosteric site might indicate the site for Sirt1 activation.

Further data

Item Type: Article in a journal
Refereed: Yes
Additional notes: PubMed-ID: 24211137
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: 20 Apr 2015 12:57
Last Modified: 18 Apr 2018 11:21
URI: https://eref.uni-bayreuth.de/id/eprint/10425