3GLR
Crystal Structure of human SIRT3 with acetyl-lysine AceCS2 peptide
Summary for 3GLR
Entry DOI | 10.2210/pdb3glr/pdb |
Related | 3GLS 3GLT 3GLU |
Descriptor | NAD-dependent deacetylase sirtuin-3, mitochondrial, Acetyl-coenzyme A synthetase 2-like, mitochondrial, ZINC ION, ... (7 entities in total) |
Functional Keywords | nad dependent deacetylase, sirtuin, substrate peptide complex, hydrolase, metal-binding, mitochondrion, nad, transit peptide, ligase, hydrolase-hydrolase regulator complex, hydrolase/hydrolase regulator |
Biological source | Homo sapiens (human) More |
Total number of polymer chains | 2 |
Total formula weight | 33541.87 |
Authors | Jin, L.,Wei, W.,Jiang, Y.,Peng, H.,Cai, J.,Mao, C.,Dai, H.,Bemis, J.E.,Jirousek, M.R.,Milne, J.C.,Westphal, C.H.,Perni, R.B. (deposition date: 2009-03-12, release date: 2009-06-16, Last modification date: 2024-10-09) |
Primary citation | Jin, L.,Wei, W.,Jiang, Y.,Peng, H.,Cai, J.,Mao, C.,Dai, H.,Choy, W.,Bemis, J.E.,Jirousek, M.R.,Milne, J.C.,Westphal, C.H.,Perni, R.B. Crystal Structures of Human SIRT3 Displaying Substrate-induced Conformational Changes. J.Biol.Chem., 284:24394-24405, 2009 Cited by PubMed 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. PubMed: 19535340DOI: 10.1074/jbc.M109.014928 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (1.8 Å) |
Structure validation
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