4G1C: Human Sirt5 Bound To Succ-Idh2 And Carba-Nad

Citation:
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.
PDB ID: 4G1CDownload
MMDB ID: 102029
PDB Deposition Date: 2012/7/10
Updated in MMDB: 2012/09
Experimental Method:
x-ray diffraction
Resolution: 1.94  Å
Source Organism:
synthetic construct
Similar Structures:
Biological Unit for 4G1C: dimeric; determined by author and by software (PISA)
Molecular Components in 4G1C
Label Count Molecule
Proteins (2 molecules)
1
Nad-dependent Protein Deacylase Sirtuin-5, Mitochondrial(Gene symbol: SIRT5)
Molecule annotation
1
Succinylated Idh2 Peptide
Molecule annotation
Chemicals (2 molecules)
1
1
2
1
* Click molecule labels to explore molecular sequence information.

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