4G1C
Human SIRT5 bound to Succ-IDH2 and Carba-NAD
Summary for 4G1C
| Entry DOI | 10.2210/pdb4g1c/pdb |
| Related | 4FVT |
| Descriptor | NAD-dependent protein deacylase sirtuin-5, mitochondrial, Succinylated IDH2 peptide, ZINC ION, ... (5 entities in total) |
| Functional Keywords | sirtuin, succinylated peptide, carbanad, hydrolase |
| Biological source | Homo sapiens (human) More |
| Cellular location | Mitochondrion matrix. Isoform 1: Cytoplasm. Isoform 2: Mitochondrion: Q9NXA8 |
| Total number of polymer chains | 4 |
| Total formula weight | 60130.99 |
| Authors | |
| Primary citation | Szczepankiewicz, B.G.,Dai, H.,Koppetsch, K.J.,Qian, D.,Jiang, F.,Mao, C.,Perni, R.B. Synthesis of Carba-NAD and the Structures of Its Ternary Complexes with SIRT3 and SIRT5. J.Org.Chem., 77:7319-7329, 2012 Cited by PubMed Abstract: Carba-NAD is a synthetic compound identical to NAD except for one substitution, where an oxygen atom adjacent to the anomeric linkage bearing nicotinamide is replaced with a methylene group. Because it is inert in nicotinamide displacement reactions, carba-NAD is an unreactive substrate analogue for NAD-consuming enzymes. SIRT3 and SIRT5 are NAD-consuming enzymes that are potential therapeutic targets for the treatment of metabolic diseases and cancers. We report an improved carba-NAD synthesis, including a pyrophosphate coupling method that proceeds in approximately 60% yield. We also disclose the X-ray crystal structures of the ternary complexes of SIRT3 and SIRT5 bound to a peptide substrate and carba-NAD. These X-ray crystal structures provide critical snapshots of the mechanism by which human sirtuins function as protein deacylation catalysts. PubMed: 22849721DOI: 10.1021/jo301067e PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.944 Å) |
Structure validation
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