3GLU

Crystal Structure of Human SIRT3 with AceCS2 peptide

Summary for 3GLU

• Entry DOI: 10.2210/pdb3glu/pdb
• Related: 3GLR 3GLS 3GLT
• Descriptor: NAD-dependent deacetylase sirtuin-3, mitochondrial, Acetyl-coenzyme A synthetase 2-like, mitochondrial, SULFATE ION, ... (5 entities in total)
• Functional Keywords: nad dependent deacetylase, sirtuin, product peptide complex, hydrolase, metal-binding, mitochondrion, nad, polymorphism, transit peptide, zinc, alternative splicing, ligase, hydrolase-hydrolase regulator complex, hydrolase/hydrolase regulator
• Biological source: Homo sapiens (human); More
• Cellular location: Mitochondrion matrix: Q9NTG7 Q9NUB1
• Total number of polymer chains: 2
• Total formula weight: 33347.73

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: 2023-09-06)

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

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: 19535340
DOI: 10.1074/jbc.M109.014928

Experimental method

X-RAY DIFFRACTION (2.5 Å)