期刊
NATURE COMMUNICATIONS
卷 7, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms10912
关键词
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资金
- Australian Research Council (ARC)
- National Health and Medical Research Council (NHMRC)
- Victorian Government's Operational Infrastructure
The metabolic stress-sensing enzyme AMP-activated protein kinase (AMPK) is responsible for regulating metabolism in response to energy supply and demand. Drugs that activate AMPK may be useful in the treatment of metabolic diseases including type 2 diabetes. We have determined the crystal structure of AMPK in complex with its activator 5-(5-hydroxyl-isoxazol-3-yl)-furan-2-phosphonic acid (C2), revealing two C2-binding sites in the gamma-subunit distinct from nucleotide sites. C2 acts synergistically with the drug A769662 to activate AMPK alpha 1-containing complexes independent of upstream kinases. Our results show that dual drug therapies could be effective AMPK-targeting strategies to treat metabolic diseases.
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