Yuan Li,Suqing Wang,Yutong Du,Di Lian,Jingjing Cui,Xue Zhang,Zihan Qu,Li Li
In this work, the inhibition effects of oroxyloside on two α -amylase from porcine pancreas (PPA) and Bacillus subtilis (BSA), as well as two α -glucosidase from Aspergillus niger (ANG) and Saccharomyces cerevisiae (SCG), were systematically compared using spectral analysis, computer simulation, and mm-PBSA calculation. Oroxyloside displayed the most potent inhibitory activity on ANG, followed by PPA, BSA, and SCG. Meanwhile, oroxyloside exhibited a mixed-type inhibition against BSA, PPA, ANG, and SCG. Oroxyloside interacted with enzyme residues mainly by hydrogen bonds and van der Waals forces, leading to the changes in the microenvironment and the secondary structure changes of enzymes, and ultimately exerting inhibitory effects. The optimal binding modes and the stability of four complexes were predicted by computer simulation. The free energy decomposition of critical residues was calculated using mm-PBSA. Oroxyloside was identified as a potential inhibitor of four enzymes, exhibiting significantly stronger inhibitory activity than acarbose.
Fuqiang Liang,Keyu Meng,Xinran Pu,Yubo Cao,Yumeng Shi,Jiayi Shi
This study investigated the molecular mechanism underlying the binding interaction between apigenin (API) and α-glucosidase (α-glu) by a combination of experimental techniques and computational simulation strategies. The spontaneously formation of stable API-α-glu complex was mainly driven by hydrogen bonds and hydrophobic forces, leading to a static fluorescence quenching of α-glu. The binding of API induced secondary structure and conformation changes of α-glu, decreasing the surface hydrophobicity of protein. Computational simulation results demonstrated that API could bind into the active cavity of α-glu via its interaction with active residues at the binding site. The important roles of key residues responsible for the binding stability and affinity between API and α-glu were further revealed by MM/PBSA results. In addition, it can be found that the entrance of active site tended to close after API binding as a result of its interaction with gate keeping residues. Furthermore, the structural basis for the binding interaction behavior of API was revealed and visualized by weak interaction analysis. The findings of our study revealed atomic-level mechanism of the interaction between API, which might shed light on the development of better inhibitors.
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