title: The ɛ-Amino Group of Protein Lysine Residues Is Highly Susceptible to Nonenzymatic Acylation by Several Physiological Acyl-CoA Thioesters.
abstract: Mitochondrial enzymes implicated in the pathophysiology of diabetes, cancer, and metabolic syndrome are highly regulated by acetylation. However, mitochondrial acetyltransferases have not been identified. Here, we show that acetylation and also other acylations are spontaneous processes that depend on pH value, acyl-CoA concentration and the chemical nature of the acyl residue. In the case of a peptide derived from carbamoyl phosphate synthetase 1, the rates of succinylation and glutarylation were up to 150 times than for acetylation. These results were confirmed by using the protein substrate cyclophilin A (CypA). Deacylation experiments revealed that SIRT3 exhibits deacetylase activity but is not able to remove any of the succinyl groups from CypA, whereas SIRT5 is an effective protein desuccinylase. Thus, the acylation landscape on lysine residues might largely depend on the enzymatic activity of specific sirtuins, and the availability and reactivity of acyl-CoA compounds.
authors.affiliation: Department of Enzymology, Institute of Biochemistry and Biotechnology, Martin-Luther-University Halle-Wittenberg, Kurt-Mothes-Strasse 3, 06120, Halle, Germany.
authors.forename: Zeljko
authors.initials: Z
authors.lastname: Simic
authors.affiliation: Department of Enzymology, Institute of Biochemistry and Biotechnology, Martin-Luther-University Halle-Wittenberg, Kurt-Mothes-Strasse 3, 06120, Halle, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Weiwad
authors.affiliation: Department of Enzymology, Institute of Biochemistry and Biotechnology, Martin-Luther-University Halle-Wittenberg, Kurt-Mothes-Strasse 3, 06120, Halle, Germany.
authors.forename: Angelika
authors.initials: A
authors.lastname: Schierhorn
authors.affiliation: Department of Biochemistry, University of Bayreuth, Universitätsstraße 30, 95440, Bayreuth, Germany.
authors.forename: Clemens
authors.initials: C
authors.lastname: Steegborn
authors.affiliation: Department of Enzymology, Institute of Biochemistry and Biotechnology, Martin-Luther-University Halle-Wittenberg, Kurt-Mothes-Strasse 3, 06120, Halle, Germany. mike.schutkowski@biochemtech.uni-halle.de.
authors.forename: Mike
authors.initials: M
authors.lastname: Schutkowski
mesh_terms: D000214:Acyl Coenzyme A / Q000378:metabolism*; D000215:Acylation; D000588:Amines / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray; D021984:Cyclophilin A / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008239:Lysine / Q000737:chemistry / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D008968:Molecular Conformation; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry; D056566:Sirtuin 3 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D037761:Sirtuins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013816:Thermodynamics
chemical_list: D000214:Acyl Coenzyme A; D000588:Amines; D010455:Peptides; D011994:Recombinant Proteins; C508544:SIRT5 protein, human; D056566:Sirtuin 3; D037761:Sirtuins; D021984:Cyclophilin A; D008239:Lysine
keywords: acetyl coenzyme A; acylation; protein modifications; sirtuin; succinyl coenzyme A