at Google ScholarTitle 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
(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: | 02 Nov 2023 14:08 |
| URI: | https://eref.uni-bayreuth.de/id/eprint/10431 |