期刊
COMMUNICATIONS BIOLOGY
卷 4, 期 1, 页码 -出版社
NATURE RESEARCH
DOI: 10.1038/s42003-021-01705-1
关键词
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资金
- MEXT KAKENHI from the Ministry of Education, Culture, Sport, Science and Technology (MEXT) of Japan [JP18H02151, JP19H03045, JP19H05771]
- Platform Project for Supporting Drug Discovery and Life Science Research (Basis for Supporting Innovative Drug Discovery and Life Science Research (BINDS)) from AMED [JP20am0101107, 2610]
KPMF-8 can activate SIRT1 more effectively than resveratrol by enhancing the binding affinity with Ac-p53 peptide.
Sirtuin 1 (SIRT1), an NAD(+)-dependent deacetylase, is a crucial regulator that produces multiple physiological benefits, such as the prevention of cancer and age-related diseases. SIRT1 is activated by sirtuin-activating compounds (STACs). Here, we report that quercetin 3,5,7,3,4 '-pentamethyl ether (KPMF-8), a natural STAC from Thai black ginger Kaempferia parviflora, interacts with SIRT1 directly and stimulates SIRT1 activity by enhancing the binding affinity of SIRT1 with Ac-p53 peptide, a native substrate peptide without a fluorogenic moiety. The binding affinity between SIRT1 and Ac-p53 peptide was enhanced 8.2-fold by KPMF-8 but only 1.4-fold by resveratrol. The specific binding sites of KPMF-8 to SIRT1 were mainly localized to the helix2-turn-helix3 motif in the N-terminal domain of SIRT1. Intracellular deacetylase activity in MCF-7 cells was promoted 1.7-fold by KPMF-8 supplemented in the cell medium but only 1.2-fold by resveratrol. This work reveals that KPMF-8 activates SIRT1 more effectively than resveratrol does.
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