title: Sanguinarine is an allosteric activator of AMP-activated protein kinase.
abstract: We found that a natural product, Sanguinarine, directly interacts with AMPK and enhances its enzymatic activity. Cell-based assays confirmed that cellular AMPK and the downstream acetyl-CoA carboxylase (ACC) were phosphorylated after Sanguinarine treatment. Sanguinarine was shown to exclusively activate AMPK holoenzymes containing α1γ1 complexes, and it activated both β1- and β2-containing isotypes of AMPK. Furthermore, a docking study suggested that Sanguinarine binds AMPK at the cleft between the β and γ domains whereas the physiological activator, AMP, binds at the well-characterized γ domain pocket. In summary, we report that Sanguinarine is a novel, direct activator of AMPK that binds by a unique allosteric mechanism different from that of the natural AMPK ligand, AMP, and other known AMPK activators. These studies have direct applications to the pharmacological study of AMPK activation and the potential development of new therapeutics.
authors: Sookmyung Women's University, Department of Biological Sciences, Research Center for Women's Diseases, Hyochangwongil 52, Yongsan-gu, Seoul 140-742, Republic of Korea.
authors: Jiwon
authors: J
authors: Choi
authors: Ningning
authors: N
authors: He
authors: Mi-Kyung
authors: MK
authors: Sung
authors: Young
authors: Y
authors: Yang
authors: Sukjoon
authors: S
authors: Yoon
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D000494:Allosteric Regulation / Q000187:drug effects; D053119:Benzophenanthridines / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007546:Isoquinolines / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D008958:Models, Molecular; D011487:Protein Conformation
chemical_list: D053119:Benzophenanthridines; D007546:Isoquinolines; C005705:sanguinarine; D055372:AMP-Activated Protein Kinases