Comparative Analysis of the Bonding Modes between Two Antidiabetic Drugs with beta-Glucosidases from Different Species

Abstract

Qi, et al.: Analysis of Bonding Modes between Antidiabetic Drugs with β-Glucosidases β-glucosidase is one of the critical enzymes to the type 2 diabetes, which belongs to a large family of glycoside hydrolases. In this article, we attempted to explore the binding modes between two drugs and β-glucosidases by comparing their bonding modes with β-glucosidases from different species. Results showed that the binding orientations and geometrical conformation of synthetic drug (miglitol) and natural product (quercetin) were all different in all active sites, which may be related to the flexibility of the molecules. Compared with the conformations obtained by density functional theory calculations at the B3LYP/6-31G* level, the docking conformations indicated that the-CH 2 CH 2 OH group of miglitol and the B ring of quercetin were the most critical groups to the stabilities in the active sites. Finally, protein sequence alignment was performed under default parameters. Although the sequence similarity is not very high between these β-glucosidases, the residues related to the active sites were conservative; especially the one involved in H-bond interactions between three species, namely soil metagenome, Micrococcus antarcticus and termite Neotermes koshunensis.

Antidiabetic Activity and In Silico Molecular Docking of Polyphenols from Ammannia baccifera L. subsp. Aegyptiaca (Willd.) Koehne Waste: Structure Elucidation of Undescribed Acylated Flavonol Diglucoside

“…Molecular docking analysis was used to demarcate the activity of the tested compounds against digestive enzymes. Previous studies reported that phenolic compounds and flavonoids were able to bind to the pockets of α -amylase, β -glucosidase and pancreatic lipase, forming enzyme-inhibitors complexes [ 20 , 21 , 22 ]. Furthermore, the researchers evaluated the potential antidiabetic activity of the flowering whole plant AEEE in diabetic rats in order to assess its antidiabetic effects.…”

Effects of Hydroxyl Group on the Interaction of Carboxylated Flavonoid Derivatives with S. Cerevisiae α-Glucosidase

“…Homology modeling was proposed by using the crystal structure of S.cerevisiae isomaltase as the template [34,35]. By using PROCHECK, the final structure of α-glucosidase generated from homology modeling was evaluated and suggested reliable results [36,37]. It can be seen from the Ramachandran plot that 87.5% of residues of the final 3D structure lay in most favored regions (Supplementary Fig.…”

Antidiabetic and anti-obesity acylated flavonol diglucoside from Ammannia baccifera L. subsp. aegyptiaca (Willd.) Koehne Waste

“…A previous study found that quercetin xed in the binding pocket of β-glucosidase mainly through hydrogen bonds and hydrophobic interactions between the complexes. The residues involved in H-bonds were mainly polar amino acids, such as Trp442, Gln57 and Asn426 [30]. The molecular docking illustrated that MGGG bind strongly to β-glucosidase catalytic site with an energy binding of -8.98 kcal/mol.…”