3GLU: Crystal Structure Of Human Sirt3 With Acecs2 Peptide

Citation:
Abstract
SIRT3 is a major mitochondrial NAD(+)-dependent protein deacetylase playing important roles in regulating mitochondrial metabolism and energy production and has been linked to the beneficial effects of exercise and caloric restriction. SIRT3 is emerging as a potential therapeutic target to treat metabolic and neurological diseases. We report the first sets of crystal structures of human SIRT3, an apo-structure with no substrate, a structure with a peptide containing acetyl lysine of its natural substrate acetyl-CoA synthetase 2, a reaction intermediate structure trapped by a thioacetyl peptide, and a structure with the dethioacetylated peptide bound. These structures provide insights into the conformational changes induced by the two substrates required for the reaction, the acetylated substrate peptide and NAD(+). In addition, the binding study by isothermal titration calorimetry suggests that the acetylated peptide is the first substrate to bind to SIRT3, before NAD(+). These structures and biophysical studies provide key insight into the structural and functional relationship of the SIRT3 deacetylation activity.
PDB ID: 3GLUDownload
MMDB ID: 73353
PDB Deposition Date: 2009/3/12
Updated in MMDB: 2011/10
Experimental Method:
x-ray diffraction
Resolution: 2.5  Å
Source Organism:
Similar Structures:
Biological Unit for 3GLU: tetrameric; determined by software (PISA)
Molecular Components in 3GLU
Label Count Molecule
Proteins (4 molecules)
2
Nad-dependent Deacetylase Sirtuin-3, Mitochondrial(Gene symbol: SIRT3)
Molecule annotation
2
Acetyl-coenzyme a Synthetase 2-like, Mitochondrial(Gene symbol: ACSS1)
Molecule annotation
Chemicals (6 molecules)
1
4
2
2
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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