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A Peptide Derived from G0/G1 Switch Gene 2 Acts as Noncompetitive Inhibitor of Adipose Triglyceride Lipase
Authors:Ines K Cerk  Barbara Salzburger  Andras Boeszoermenyi  Christoph Heier  Christoph Pillip  Matthias Romauch  Martina Schweiger  Irina Cornaciu  Achim Lass  Robert Zimmermann  Rudolf Zechner  Monika Oberer
Institution:From the Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria
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.
Keywords:Adipose Triglyceride Lipase (ATGL)  Enzyme Inhibitor  Lipid  Lipid Metabolism  Lipolysis  Peptides  Atglistatin  G0/G1 Switch Gene 2 (G0S2)  hGW2052  Noncompetitive Inhibition
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