Cerk Ines K, Salzburger Barbara, Boeszoermenyi Andras, Heier Christoph, Pillip Christoph, Romauch Matthias, Schweiger Martina, Cornaciu Irina, Lass Achim, Zimmermann Robert, Zechner Rudolf, Oberer Monika
From the Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria.
From the Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria
J Biol Chem. 2014 Nov 21;289(47):32559-70. doi: 10.1074/jbc.M114.602599. Epub 2014 Sep 25.
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.
蛋白质G0/G1转换基因2（G0S2）是一种小的碱性蛋白质，作为脂肪甘油三酯脂肪酶（ATGL）的内源性抑制剂发挥作用，ATGL是细胞内脂肪分解的关键酶。在本研究中，我们鉴定出G0S2中覆盖第20位赖氨酸至第52位丙氨酸残基的短序列，该序列仍完全能够抑制小鼠和人类的ATGL。我们发现，对应于该区域的合成肽在纳摩尔范围内以非竞争性方式抑制ATGL。该肽对ATGL具有高度选择性，不抑制其他脂肪酶，包括激素敏感性脂肪酶、单酰甘油脂肪酶、脂蛋白脂肪酶以及含马铃薯Patatin结构域的磷脂酶6和7。由于脂肪分解增加与代谢紊乱的发展有关，G0S2衍生肽对ATGL的抑制作用可能代表一种调节脂肪分解的新型治疗工具。
