4c78 | pdb_00004c78

Complex of human Sirt3 with Bromo-Resveratrol and ACS2 peptide

spinqualitylabelsall models 4c78, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4c78 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: BVB, ZN NonStd Res: ALY Related: 4c7b Activity: Acetate--CoA ligase, with EC number 6.2.1.1 Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed Sirtuins are protein deacetylases regulating aging processes and various physiological functions. Resveratrol, a polyphenol found in red wine, activates human Sirt1 and inhibits Sirt3, and it can mimic calorie restriction effects, such as lifespan extension in lower organisms. The mechanism of Sirtuin modulation by resveratrol is not well understood. We used 4'-bromo-resveratrol (5-(2-(4-hydroxyphenyl)vinyl)-1,3-benzenediol) to study Sirt1 and Sirt3 modulation. Despite its similarity to the Sirt1 activator resveratrol, the compound potently inhibited both, Sirt1 and Sirt3. Crystal structures of Sirt3 in complex with a fluorophore-labeled and with a native substrate peptide, respectively, in presence of 4'-bromo-resveratrol reveal two compound binding sites. Biochemical studies identify the internal site and substrate competition as the mechanism for inhibition, providing a drug target site, and homology modeling suggests that the second, allosteric site might indicate the site for Sirt1 activation. Crystal structures of sirt3 complexes with 4'-bromo-resveratrol reveal binding sites and inhibition mechanism.,Nguyen GT, Gertz M, Steegborn C Chem Biol. 2013 Nov 21;20(11):1375-85. doi: 10.1016/j.chembiol.2013.09.019. Epub , 2013 Nov 7. PMID:24211137 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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