Sirtuin 3 (SIRT3) Protein Regulates Long-chain Acyl-CoA Dehydrogenase by Deacetylating Conserved Lysines Near the Active Site
作者： Sivakama S. Bharathi , Yuxun Zhang , Al-Walid Mohsen , Radha Uppala , Manimalha Balasubramani
关键词: Acyl CoA dehydrogenase 、 Dehydrogenase 、 Biology 、 Biochemistry 、 Lysine 、 Beta oxidation 、 Long-chain acyl-CoA dehydrogenase 、 Active site 、 Cofactor 、 Acetylation
摘要: Long-chain acyl-CoA dehydrogenase (LCAD) is a key mitochondrial fatty acid oxidation enzyme. We previously demonstrated increased LCAD lysine acetylation in SIRT3 knockout mice concomitant with reduced activity and oxidation. To study the effects of on determine sirtuin 3 (SIRT3) target sites, we chemically acetylated recombinant LCAD. Acetylation impeded substrate binding catalytic efficiency. Deacetylation partially restored activity. Residues Lys-318 Lys-322 were identified as SIRT3-targeted lysines. Arginine substitutions at prevented acetylation-induced loss. flank residues Arg-317 Phe-320, which are conserved among all dehydrogenases coordinate enzyme-bound FAD cofactor active site. propose that Lys-318/Lys-322 causes conformational change reduces hydride transfer from to FAD. Medium-chain 9, two related enzymes lysines positions equivalent Lys-318/Lys-322, also efficiently deacetylated by following chemical acetylation. These results suggest acetylation/deacetylation mode regulating The same mechanism may regulate other dehydrogenases.
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