Gao Feng, Qian Yue-Jiao, Chen Fei-Hu, Zhu Hai-Bo
a State Key Laboratory for Bioactive Substance and Function of Natural Medicines, Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing 100050 , China.
b Anhui Key Laboratory of Bioactivity of Natural Products, School of Pharmacy, Anhui Medical University , Hefei 230032 , China.
J Asian Nat Prod Res. 2019 Sep;21(9):916-927. doi: 10.1080/10286020.2018.1484454. Epub 2018 Sep 6.
To compare the stimulation and binding characteristics of adenosine analogs including AMP, IMM-H007, and M1, to AMPK, and to explore the potential mechanism underlying the regulation effect of adenosine analogs on AMPK activity, [γ-P]ATP assay, circular dichroism experiments and molecular docking test were performed. We found that the interactions with Thr86, Thr88, and His150 in site 1 are probably the reason why the affinities of IMM-H007, M1, and adenosine are comparable but their allosteric activation on AMPK varies greatly, partly interpreting the mechanism of AMPK activity regulated by adenosine analogs.
为比较包括AMP、IMM-H007和M1在内的腺苷类似物对AMPK的刺激和结合特性，并探索腺苷类似物对AMPK活性调节作用的潜在机制，进行了[γ-P]ATP测定、圆二色性实验和分子对接测试。我们发现，与1位点的Thr86、Thr88和His150的相互作用可能是IMM-H007、M1和腺苷亲和力相当但它们对AMPK的变构激活差异很大的原因，部分解释了腺苷类似物调节AMPK活性的机制。
