Abstract: This study aimed to investigate the interaction between erianin and human pyruvate carboxylase(hPC), and thus lay a foundation for elucidating its pharmacology and toxicology. Computer molecular simulation docking was employed to predict the binding and interaction intensity of erianin and hPC, furthermore, mitochondrial protein incubation system was used to verify the effect of erianin on hPC activity in vitro. Molecular docking results showed that erianin could bind to hPC at multiple sites. The best binding poses were AD interface and BC interface of the tetramer protein, the trimethoxyphenyl group of erianin interacted with the hPC methionine(B: 804) residue via a π-sulfur and a π-alkyl interaction, the main benzene ring interacted with the aspartic acid(C: 774) residue of hPC through hydrogen bonding and π-anion interaction, and there were also multiple methoxy groups that had a hydrocarbon-non-bond interaction with hPC. Consistently, In vitro inhibition experiments showed that erianin had a significant inhibitory effect on hPC in a dose-dependent manner. Collectively, the experiments showed that the binding of erianin and hPC, and also erianin treatment inhibited the enzyme activity of hPC.

Key words: erianin, pyruvate carboxylase, molecular docking, interaction