4UTV
Crystal structure of zebrafish Sirtuin 5 in complex with 3-phenyl- succinylated CPS1-peptide
Summary for 4UTV
| Entry DOI | 10.2210/pdb4utv/pdb |
| Related | 4UTN 4UTR 4UTX 4UTZ 4UU7 4UU8 4UUA 4UUB |
| Descriptor | NAD-DEPENDENT PROTEIN DEACYLASE SIRTUIN-5, MITOCHONDRIAL, CARBAMOYLPHOSPHATE SYNTHETASE I, ZINC ION, ... (9 entities in total) |
| Functional Keywords | hydrolase, regulatory enzyme, deacylase, mitochondrial, rossmann-fold, zinc-binding |
| Biological source | DANIO RERIO (ZEBRAFISH) More |
| Cellular location | Mitochondrion (By similarity): Q6DHI5 |
| Total number of polymer chains | 3 |
| Total formula weight | 62675.30 |
| Authors | Pannek, M.,Gertz, M.,Steegborn, C. (deposition date: 2014-07-23, release date: 2014-08-20, Last modification date: 2024-01-31) |
| Primary citation | Roessler, C.,Nowak, T.,Pannek, M.,Gertz, M.,Nguyen, G.T.,Scharfe, M.,Born, I.,Sippl, W.,Steegborn, C.,Schutkowski, M. Chemical Probing of the Human Sirtuin 5 Active Site Reveals its Substrate Acyl Specificity and Peptide-Based Inhibitors. Angew.Chem.Int.Ed.Engl., 53:10728-, 2014 Cited by PubMed Abstract: 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. PubMed: 25111069DOI: 10.1002/ANIE.201402679 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.4 Å) |
Structure validation
Download full validation report
