Metformin interacts with AMPK through binding to γ subunit.
Metformin acts as an energy regulator by activating 5'-adenosine monophosphate-activated protein kinase (AMPK), which is a key player in the regulation of energy homeostasis, but it is uncertain whether AMPK is its direct target. This study aims to investigate the possible interaction between metformin and AMPK. First, we verified that metformin can promote AMPK activation and induce ACC inactivation in human HepG2 cells using western blot. Then we predicted that metformin may interact with the γ subunit of AMPK by molecular docking analysis. The fluorescence spectrum and ForteBio assays indicated that metformin has a stronger binding ability to the γ subunit of AMPK than to α subunit. In addition, interaction of metformin with γ-AMPK resulted in a decrease in the α-helicity determined by CD spectra, but relatively little change was seen with α-AMPK. These results demonstrate that metformin may interact with AMPK through binding to the γ subunit.
Department of Oncology, The 174th Hospital of the Chinese People's Liberation Army, The Affiliated Chenggong Hospital of Xiamen University, Xiamen 361003, Fujian, People's Republic of China.
Yaya
Y
Zhang
Yongjun
Y
Wang
Chuanen
C
Bao
Yingyi
Y
Xu
Huili
H
Shen
Junjie
J
Chen
Jianghua
J
Yan
Yuqiang
Y
Chen
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D008687:Metformin / Q000493:pharmacokinetics* / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects
D007004:Hypoglycemic Agents; D008687:Metformin; D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase