Titlebar

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

 

Chemical probing of the human sirtuin 5 active site reveals its substrate acyl specificity and peptide-based inhibitors.

Title data

Roessler, Claudia ; Nowak, Theresa ; Pannek, Martin ; Gertz, Melanie ; Nguyen, Giang Thi Tuyet ; Scharfe, Michael ; Born, Ilona ; Sippl, Wolfgang ; Steegborn, Clemens ; Schutkowski, Mike:
Chemical probing of the human sirtuin 5 active site reveals its substrate acyl specificity and peptide-based inhibitors.
In: Angewandte Chemie International Edition. Vol. 53 (26 September 2014) Issue 40 . - pp. 10728-10732.
ISSN 1521-3773
DOI: https://doi.org/10.1002/anie.201402679

Abstract in another language

Sirtuins are NAD(+)-dependent deacetylases acting as sensors in metabolic pathways and stress response. In mammals there are seven isoforms. The mitochondrial sirtuin 5 is a weak deacetylase but a very efficient demalonylase and desuccinylase; however, its substrate acyl specificity has not been systematically analyzed. Herein, we investigated a carbamoyl phosphate synthetase 1 derived peptide substrate and modified the lysine side chain systematically to determine the acyl specificity of Sirt5. From that point we designed six potent peptide-based inhibitors that interact with the NAD(+) binding pocket. To characterize the interaction details causing the different substrate and inhibition properties we report several X-ray crystal structures of Sirt5 complexed with these peptides. Our results reveal the Sirt5 acyl selectivity and its molecular basis and enable the design of inhibitors for Sirt5.

Further data

Item Type: Article in a journal
Refereed: Yes
Additional notes: PubMed-ID: 25111069
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 14:21
Last Modified: 18 Apr 2018 11:21
URI: https://eref.uni-bayreuth.de/id/eprint/10431