title: A peptide derived from G0/G1 switch gene 2 acts as noncompetitive inhibitor of adipose triglyceride lipase.
abstract: The protein G0/G1 switch gene 2 (G0S2) is a small basic protein that functions as an endogenous inhibitor of adipose triglyceride lipase (ATGL), a key enzyme in intracellular lipolysis. In this study, we identified a short sequence covering residues Lys-20 to Ala-52 in G0S2 that is still fully capable of inhibiting mouse and human ATGL. We found that a synthetic peptide corresponding to this region inhibits ATGL in a noncompetitive manner in the nanomolar range. This peptide is highly selective for ATGL and does not inhibit other lipases, including hormone-sensitive lipase, monoacylglycerol lipase, lipoprotein lipase, and patatin domain-containing phospholipases 6 and 7. Because increased lipolysis is linked to the development of metabolic disorders, the inhibition of ATGL by G0S2-derived peptides may represent a novel therapeutic tool to modulate lipolysis.
authors.affiliation: From the Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria.
authors.forename: Ines K
authors.initials: IK
authors.lastname: Cerk
authors.affiliation: From the Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria.
authors.forename: Barbara
authors.initials: B
authors.lastname: Salzburger
authors.affiliation: From the Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria.
authors.forename: Andras
authors.initials: A
authors.lastname: Boeszoermenyi
authors.affiliation: From the Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria.
authors.forename: Christoph
authors.initials: C
authors.lastname: Heier
authors.affiliation: From the Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria.
authors.forename: Christoph
authors.initials: C
authors.lastname: Pillip
authors.affiliation: From the Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria.
authors.forename: Matthias
authors.initials: M
authors.lastname: Romauch
authors.affiliation: From the Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria.
authors.forename: Martina
authors.initials: M
authors.lastname: Schweiger
authors.affiliation: From the Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria.
authors.forename: Irina
authors.initials: I
authors.lastname: Cornaciu
authors.affiliation: From the Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria.
authors.forename: Achim
authors.initials: A
authors.lastname: Lass
authors.affiliation: From the Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria.
authors.forename: Robert
authors.initials: R
authors.lastname: Zimmermann
authors.affiliation: From the Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Zechner
authors.affiliation: From the Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria m.oberer@uni-graz.at.
authors.forename: Monika
authors.initials: M
authors.lastname: Oberer
mesh_terms: D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008049:Lipase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D010455:Peptides / Q000235:genetics / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism*; D000217:Acyltransferases
chemical_list: D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase; D018797:Cell Cycle Proteins; D008049:Lipase; D010455:Peptides; D011994:Recombinant Proteins; C508073:G0S2 protein, human; C492986:Abhd5 protein, mouse; C494794:PNPLA2 protein, human; D000217:Acyltransferases; C494445:PNPLA2 protein, mouse
keywords: Adipose Triglyceride Lipase (ATGL); Atglistatin; Enzyme Inhibitor; G0/G1 Switch Gene 2 (G0S2); Lipid; Lipid Metabolism; Lipolysis; Noncompetitive Inhibition; Peptides; hGW2052